Roxanne Nelson, RN, BSN

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

A version of this article originally appeared on Medscape.com.

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

A version of this article originally appeared on Medscape.com.

In an update to its 2016 recommendations for skin cancer screening, the U.S. Preventive Services Task Force (USPSTF) has once again determined that there is not enough evidence to recommend for or against screening with a visual skin exam in adolescents and adults without symptoms.

This final recommendation applies to the general public and is not meant for those at higher risk, such as people with a family history of skin cancer or who have any signs or symptoms, such as irregular moles.

“The new recommendations are consistent with those from 2016, and we are unable to balance benefits and harms,” said Task Force member Katrina Donahue, MD, MPH, professor and vice chair of research in the department of family medicine at the University of North Carolina, Chapel Hill. “Unfortunately, there is not enough evidence to recommend for or against screening, and health care professionals should use their judgment when deciding whether or not to screen.”

Dr. Donahue told this news organization that this is a call for more research: “Our recommendations are for patients who present to primary care without symptoms, and after a careful assessment of benefit and harms, we didn’t have evidence to push us towards screening as a benefit. We did look at data from two large screening programs, but they were from Europe and not representative of the U.S. population. They also did not show a benefit for reducing melanoma-related mortality.”

The USPSTF final recommendation statement and corresponding evidence summary have been published online in JAMA, as well as on the USPSTF website.

Skin cancer is the most commonly diagnosed cancer in the United States, but there are different types that vary in their incidence and severity. Basal and squamous cell carcinomas are the most common types of skin cancer, but they infrequently lead to death or substantial morbidity, notes the USPTSF. Melanomas represent about 1% of skin cancer and cause the most skin cancer deaths. An estimated 8,000 individuals in the United States will die of melanoma in 2023.

There are racial differences in melanoma incidence; it is about 30 times more common in White versus Black persons, but disease in persons with darker skin color tends to be diagnosed at a later stage. These disparities may be due to differences in risk factors, access to care, and clinical presentation.

In an accompanying editorial, Maryam M. Asgari, MD, MPH, of the department of dermatology, Massachusetts General Hospital, Boston, and Lori A. Crane, PhD, MPH, of the Colorado School of Public Health, University of Colorado, Aurora, point out that people with darker skin phenotypes also tend to be affected by skin cancers that are not associated with UV radiation, such as acral melanoma, which arises on the palms and soles, and skin cancers that arise in areas of chronic inflammation, such as wounds.

Review of evidence

The USPSTF commissioned a systematic review to evaluate the benefits and harms of screening for skin cancer in asymptomatic adolescents and adults, including evidence for both keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma) and cutaneous melanoma.

Foundational evidence showed that the sensitivity of visual skin examination by a clinician to detect melanoma ranged from 40% to 70% and specificity ranged from 86% to 98%. Evidence that evaluated the diagnostic accuracy of visual skin examination to detect keratinocyte carcinoma was limited and inconsistent. There were no new studies reporting on diagnostic accuracy for an asymptomatic screening population.

The USPSTF also reviewed 20 studies in 29 articles (n = 6,053,411). This included three nonrandomized studies evaluating two skin cancer screening programs in Germany, but results were inconsistent. In addition, the ecological and nonrandomized design of the studies limited the conclusions that could be drawn and the applicability to a U.S. population was difficult to assess because of differences in population diversity and health care delivery in the United States.

Other nonrandomized studies that looked at various outcomes, such as harms and stage at diagnosis and melanoma or all-cause mortality, also did not provide sufficient evidence to support screening.
 

Research is needed

In a second accompanying editorial published in JAMA Dermatology, Adewole S. Adamson, MD, MPP, of the division of dermatology and dermatologic surgery at the University of Texas, Austin, pointed out that unlike other cancer screening programs, such as those for breast, colon, and prostate cancer, skin cancer screening programs are somewhat less organized.

The other programs focus on defined groups of the population, generally with easily identifiable characteristics such as age, sex, and family history, and importantly, there are always defined ages for initiation and halting of screening and intervals for screening frequency. None of these basic screening parameters have been widely adopted among dermatologists in the United States, he wrote. “One important reason why skin cancer screening has remained inconsistent is that it is not covered by Medicare or by many commercial insurance companies,” Dr. Adamson told this news organization. “The test, in this case the skin exam, is often performed as part of a routine dermatology visit.”

Dermatologists should take the lead on this, he said. “Dermatologists should push for a high quality prospective clinical trial of skin cancer screening, preferably in a high-risk population.”

Dr. Donahue agrees that research is needed, as noted in the recommendation. For example, studies are needed demonstrating consistent data of the effects of screening on morbidity and mortality or early detection of skin cancer, and clearer descriptions of skin color and inclusion of a full spectrum of skin colors in study participants. Clinical research is also needed on outcomes in participants that reflect the diversity of the U.S. population.

“I hope funding agencies will be interested in this area of study,” she said. “We put out the whole systematic review and point out the gaps. We need consistent evidence in detecting cancer early and reducing complications from skin cancer.”

The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.

None of the USPSTF authors report any disclosures. Dr. Asgari reported receiving royalties from UpToDate. Dr. Crane did not make any disclosures. Dr. Adamson reported serving as an expert reviewer for the U.S. Preventive Services Task Force skin cancer screening report, as well as support from the Robert Wood Johnson Foundation, the Dermatology Foundation Public Health Career Development Award, the National Institutes of Health, the American Cancer Society, and Meredith’s Mission for Melanoma.

A version of this article originally appeared on Medscape.com.

Women harboring BRCA1/2 gene mutations are at high risk for breast cancer, and thus it’s recommended they undergo annual breast MRI screening in addition to mammogram screening.
 

However, some women are finding that their insurer is refusing to cover the cost of the MRI.

A new study exploring this issue was presented at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

“Despite guidelines supporting annual breast MRI for screening in patients with gBRCA1/2, insurance denials were present in 11% of patients,” said lead author Sushmita Gordhandas, MD, a gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. “In a high-resource setting, up to 14% of patients who were denied coverage did not undergo recommended MRI screening.”

She also pointed out that the rate of denials was rising. “Compared to 2020, there were significantly more denials, and denials on appeal, in 2021,” Dr. Gordhandas said. “This suggested worsening barriers and added burden on health care systems.”

The addition of MRI to mammography is a standard recommendation for women with BRCA mutations, she pointed out, as it has been shown improve detection of early disease and decrease interval cancer development.

An expert not involved in the study noted that the recommendation for annual MRI screening in women at high risk for breast cancer is “substantiated by many publications, including multiple prospective clinical trials.”

Linda Moy, MD, a radiologist at NYU Langone’s Perlmutter Cancer Center and professor of radiology at NYU Grossman School of Medicine, both in New York, noted that the American Cancer Society’s Guidelines for screening breast MRI recommends annual breast MRI in women with a lifetime risk of greater than 20% – which includes women who are BRCA carriers – and recommends the screening begins at age 30.

“The lifetime breast cancer risk is 72% among BRCA1 and 69% among BRCA2 carriers,” she said, adding that the “American College of Radiology also recommends for BRCA carriers to undergo annual screening MRI at age 30.”

The National Comprehensive Cancer Network recommends that women at high risk for breast cancer undergo a mammogram and breast MRI every year starting at age 25 to 40, depending on the type of gene mutation, noted Dr. Gordhandas. “These guidelines are consistent with those from American College of Obstetricians and Gynecologists, the American Cancer Society, and the American College of Radiology.”
 

Denials increased over time

For the study, Dr. Gordhandas and colleagues looked at the frequency of insurance denials for indicated breast MRI screening in women with germline BRCA1/2 pathogenic variants, and also looked at recent trends in denials over time.

The cohort comprised 682 women with BRCA1/2 gene mutations who were followed in a specialized high-risk breast cancer clinic, and who had breast MRIs ordered from 2020 to 2021. They were then cross-referenced with a database of insurance denials. Radiology records were also accessed to determine if screening breast MRIs had been performed in 2020 and 2021, and rates of MRI denials and results after appeals were determined. The rates between the 2 years were then compared.

The team found that overall, 73 women (11%) had an MRI denied. The median age of women who received a denial was 38 years, whereas those who had it approved was 44 years. “Patients with denials were significantly younger and more likely to be in the Medicaid population,” said Dr. Gordhandas.

In 2020, 29 breast MRIs (5%) were denied, and on appeal, 8 (28%) were denied and 21 (72%) approved. The number of denials rose in 2021 but approvals remained the same; 45 breast MRIs were denied (8%); on appeal, 23 (51%) were denied, and 22 (49%) approved.

Thus, noted the authors, there were significantly more denials in 2021 as compared with 2020 (P = .044), and the denials in 2021 denials were statistically more likely to be denied on appeal (P = .045).

Among the women whose coverage was denied, four (14%) in 2020 and five (11%) in 2021 did not have an MRI screening performed. And within this group, 17 women (2.5%) received a diagnosis of cancer; 12 (1.8%) had invasive carcinoma, and 5 (0.7%) had ductal carcinoma in situ (DCIS). One patient with DCIS had an MRI denial prior to receiving her diagnosis.

“The top reasons given for denials were that they were outside the approved time frame, authorization on file for a similar study, and that the clinician failed to show medical necessity,” she explained.

Additional data are needed to establish a trend. “We are working to increase the approval time frame, which is currently 45 days, and provide resources for the patient to deal with denials,” Dr. Gordhandas added. “We also have to advocate for updates to [U.S. Preventive Services Task Force] screening recommendations in high-risk patients.”

Dr. Gordhandas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women harboring BRCA1/2 gene mutations are at high risk for breast cancer, and thus it’s recommended they undergo annual breast MRI screening in addition to mammogram screening.
 

However, some women are finding that their insurer is refusing to cover the cost of the MRI.

A new study exploring this issue was presented at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

“Despite guidelines supporting annual breast MRI for screening in patients with gBRCA1/2, insurance denials were present in 11% of patients,” said lead author Sushmita Gordhandas, MD, a gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. “In a high-resource setting, up to 14% of patients who were denied coverage did not undergo recommended MRI screening.”

She also pointed out that the rate of denials was rising. “Compared to 2020, there were significantly more denials, and denials on appeal, in 2021,” Dr. Gordhandas said. “This suggested worsening barriers and added burden on health care systems.”

The addition of MRI to mammography is a standard recommendation for women with BRCA mutations, she pointed out, as it has been shown improve detection of early disease and decrease interval cancer development.

An expert not involved in the study noted that the recommendation for annual MRI screening in women at high risk for breast cancer is “substantiated by many publications, including multiple prospective clinical trials.”

Linda Moy, MD, a radiologist at NYU Langone’s Perlmutter Cancer Center and professor of radiology at NYU Grossman School of Medicine, both in New York, noted that the American Cancer Society’s Guidelines for screening breast MRI recommends annual breast MRI in women with a lifetime risk of greater than 20% – which includes women who are BRCA carriers – and recommends the screening begins at age 30.

“The lifetime breast cancer risk is 72% among BRCA1 and 69% among BRCA2 carriers,” she said, adding that the “American College of Radiology also recommends for BRCA carriers to undergo annual screening MRI at age 30.”

The National Comprehensive Cancer Network recommends that women at high risk for breast cancer undergo a mammogram and breast MRI every year starting at age 25 to 40, depending on the type of gene mutation, noted Dr. Gordhandas. “These guidelines are consistent with those from American College of Obstetricians and Gynecologists, the American Cancer Society, and the American College of Radiology.”
 

Denials increased over time

For the study, Dr. Gordhandas and colleagues looked at the frequency of insurance denials for indicated breast MRI screening in women with germline BRCA1/2 pathogenic variants, and also looked at recent trends in denials over time.

The cohort comprised 682 women with BRCA1/2 gene mutations who were followed in a specialized high-risk breast cancer clinic, and who had breast MRIs ordered from 2020 to 2021. They were then cross-referenced with a database of insurance denials. Radiology records were also accessed to determine if screening breast MRIs had been performed in 2020 and 2021, and rates of MRI denials and results after appeals were determined. The rates between the 2 years were then compared.

The team found that overall, 73 women (11%) had an MRI denied. The median age of women who received a denial was 38 years, whereas those who had it approved was 44 years. “Patients with denials were significantly younger and more likely to be in the Medicaid population,” said Dr. Gordhandas.

In 2020, 29 breast MRIs (5%) were denied, and on appeal, 8 (28%) were denied and 21 (72%) approved. The number of denials rose in 2021 but approvals remained the same; 45 breast MRIs were denied (8%); on appeal, 23 (51%) were denied, and 22 (49%) approved.

Thus, noted the authors, there were significantly more denials in 2021 as compared with 2020 (P = .044), and the denials in 2021 denials were statistically more likely to be denied on appeal (P = .045).

Among the women whose coverage was denied, four (14%) in 2020 and five (11%) in 2021 did not have an MRI screening performed. And within this group, 17 women (2.5%) received a diagnosis of cancer; 12 (1.8%) had invasive carcinoma, and 5 (0.7%) had ductal carcinoma in situ (DCIS). One patient with DCIS had an MRI denial prior to receiving her diagnosis.

“The top reasons given for denials were that they were outside the approved time frame, authorization on file for a similar study, and that the clinician failed to show medical necessity,” she explained.

Additional data are needed to establish a trend. “We are working to increase the approval time frame, which is currently 45 days, and provide resources for the patient to deal with denials,” Dr. Gordhandas added. “We also have to advocate for updates to [U.S. Preventive Services Task Force] screening recommendations in high-risk patients.”

Dr. Gordhandas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women harboring BRCA1/2 gene mutations are at high risk for breast cancer, and thus it’s recommended they undergo annual breast MRI screening in addition to mammogram screening.
 

However, some women are finding that their insurer is refusing to cover the cost of the MRI.

A new study exploring this issue was presented at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

“Despite guidelines supporting annual breast MRI for screening in patients with gBRCA1/2, insurance denials were present in 11% of patients,” said lead author Sushmita Gordhandas, MD, a gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. “In a high-resource setting, up to 14% of patients who were denied coverage did not undergo recommended MRI screening.”

She also pointed out that the rate of denials was rising. “Compared to 2020, there were significantly more denials, and denials on appeal, in 2021,” Dr. Gordhandas said. “This suggested worsening barriers and added burden on health care systems.”

The addition of MRI to mammography is a standard recommendation for women with BRCA mutations, she pointed out, as it has been shown improve detection of early disease and decrease interval cancer development.

An expert not involved in the study noted that the recommendation for annual MRI screening in women at high risk for breast cancer is “substantiated by many publications, including multiple prospective clinical trials.”

Linda Moy, MD, a radiologist at NYU Langone’s Perlmutter Cancer Center and professor of radiology at NYU Grossman School of Medicine, both in New York, noted that the American Cancer Society’s Guidelines for screening breast MRI recommends annual breast MRI in women with a lifetime risk of greater than 20% – which includes women who are BRCA carriers – and recommends the screening begins at age 30.

“The lifetime breast cancer risk is 72% among BRCA1 and 69% among BRCA2 carriers,” she said, adding that the “American College of Radiology also recommends for BRCA carriers to undergo annual screening MRI at age 30.”

The National Comprehensive Cancer Network recommends that women at high risk for breast cancer undergo a mammogram and breast MRI every year starting at age 25 to 40, depending on the type of gene mutation, noted Dr. Gordhandas. “These guidelines are consistent with those from American College of Obstetricians and Gynecologists, the American Cancer Society, and the American College of Radiology.”
 

Denials increased over time

For the study, Dr. Gordhandas and colleagues looked at the frequency of insurance denials for indicated breast MRI screening in women with germline BRCA1/2 pathogenic variants, and also looked at recent trends in denials over time.

The cohort comprised 682 women with BRCA1/2 gene mutations who were followed in a specialized high-risk breast cancer clinic, and who had breast MRIs ordered from 2020 to 2021. They were then cross-referenced with a database of insurance denials. Radiology records were also accessed to determine if screening breast MRIs had been performed in 2020 and 2021, and rates of MRI denials and results after appeals were determined. The rates between the 2 years were then compared.

The team found that overall, 73 women (11%) had an MRI denied. The median age of women who received a denial was 38 years, whereas those who had it approved was 44 years. “Patients with denials were significantly younger and more likely to be in the Medicaid population,” said Dr. Gordhandas.

In 2020, 29 breast MRIs (5%) were denied, and on appeal, 8 (28%) were denied and 21 (72%) approved. The number of denials rose in 2021 but approvals remained the same; 45 breast MRIs were denied (8%); on appeal, 23 (51%) were denied, and 22 (49%) approved.

Thus, noted the authors, there were significantly more denials in 2021 as compared with 2020 (P = .044), and the denials in 2021 denials were statistically more likely to be denied on appeal (P = .045).

Among the women whose coverage was denied, four (14%) in 2020 and five (11%) in 2021 did not have an MRI screening performed. And within this group, 17 women (2.5%) received a diagnosis of cancer; 12 (1.8%) had invasive carcinoma, and 5 (0.7%) had ductal carcinoma in situ (DCIS). One patient with DCIS had an MRI denial prior to receiving her diagnosis.

“The top reasons given for denials were that they were outside the approved time frame, authorization on file for a similar study, and that the clinician failed to show medical necessity,” she explained.

Additional data are needed to establish a trend. “We are working to increase the approval time frame, which is currently 45 days, and provide resources for the patient to deal with denials,” Dr. Gordhandas added. “We also have to advocate for updates to [U.S. Preventive Services Task Force] screening recommendations in high-risk patients.”

Dr. Gordhandas reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

A version of this article first appeared on Medscape.com.

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

A version of this article first appeared on Medscape.com.

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

A version of this article first appeared on Medscape.com.

In a small cohort of patients with hematologic cancer and their caregivers, the use of a financial navigator helped secure cost savings of approximately $2,500 per person. This saving was achieved by helping participants to optimize health insurance, identify different types of assistance for out-of-pocket expenses, or apply for disability or family medical leave.

Cancer patients in the United States face complex financial issues in navigating with medical insurance companies to cover their care. This “financial toxicity” has come to be regarded as a side effect of cancer treatment.

Patients with hematologic malignancies may be particularly vulnerable to financial toxicity, owing to the nature of their treatment, which often includes bone marrow transplantation, lengthy hospital stays, and prolonged intensive follow-up, as well as potential treatment-related complications, such as graft vs. host disease.

The results from this small study suggest that using an oncology financial navigator could be helpful. But not all cancer patients have access to such a person, explained lead author Jean S. Edward, PhD, RN, associate professor in the college of nursing at the University of Kentucky, Lexington.

“Unfortunately, it’s not as common as we would like, especially in underserved areas with patient and caregiver populations that need it the most,” she said. Dr. Edward is hopeful that the results from this study, even though it is small, might help to boost use of this intervention. “OFN [oncology financial navigation] is not necessarily a cutting-edge program or ‘novel’ intervention, but the lack of programs and limitations in implementing in cancer centers does make it a gap in practice,” Dr. Edward told this news organization.

“There are gaps in evidence on how to incorporate an oncology financial navigator in current workflows and sustainability of positions, but as our study has shown, the return on investment to the health care system and/or financial benefits to patients/caregivers could help cover the cost of implementing such programs,” she said.

The study was published in JCO Oncology Practice.

The intervention used in this study, Coverage and Cost-of-Care Links (CC Links), was designed specifically to address financial toxicity among patients with hematologic cancers.

The study’s primary outcomes were defined as improvements in financial distress as well as in physical and mental quality of life.

A total of 54 patients and 32 caregivers completed the intervention and pre-/postintervention surveys. More than half of participants were women. The average age was 63 years. Less than a quarter of the patients were employed (23%), about one-third had income that was below the federal poverty level, and almost all had insurance. About 59% of the caregivers were employed.

The navigators’ functions included screening for financial toxicity using FACIT-Comprehensive Score for Financial Toxicity (COST) and the National Comprehensive Cancer Network’s Distress Thermometer and Problem List. They also helped patients to estimate cost of care, assessed health insurance coverage, and connected patients/caregivers with disease-specific resources and other external assistance programs, among other things.

Participants had an average of three in-person meetings and five telephone interactions with the financial navigator. The most common concern was in regard to high out-of-pocket costs. The most frequently provided services from the navigator were helping with financial assistance programs and grant applications. Overall, the navigator was able to obtain $124,600 in financial benefits for 48 participants, as well as money for travel ($24,000), urgent needs ($16,000), patient financial assistance ($9,100), and copay assistance grants ($75,500).

With regard to scores on the screening tools, the only significant change from pre- to postintervention was in the psychological response score, or COST. It decreased by an average of 2.30 points (P = .019; Hedges’ g = 0.33). For caregivers, there was a significant improvement in COST (average decrease, 2.97 points; P = .021; g = 0.43), material condition scores (average decrease, 0.63 points; P = .031; g = 0.39), and total financial toxicity scores (average decrease, 0.13 points; P = .041; g = 0.37).

Most of the participants gave the intervention high ratings for acceptability (89%) and appropriateness (88%).

“Standardized screening for financial toxicity in cancer care settings is essential to support early identification of financial needs that serve as barriers to care,” the authors conclude. “Close collaboration and coordination with existing services and workflows are essential for the seamless integration of OFN interventions within health systems and to help facilitate contact and communication with participants.”

The study was supported by the National Cancer Institute; the University of Kentucky’s Markey Cancer Center; the Research Communications Office of the Patient Oriented and Population Science Shared Resource Facilities; Joan Scales, LCSW, and the Psych-Oncology Program at the University of Kentucky Markey Cancer Center; and UK HealthCare’s Patient Financial Services. Dr. Edward has disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

In a small cohort of patients with hematologic cancer and their caregivers, the use of a financial navigator helped secure cost savings of approximately $2,500 per person. This saving was achieved by helping participants to optimize health insurance, identify different types of assistance for out-of-pocket expenses, or apply for disability or family medical leave.

Cancer patients in the United States face complex financial issues in navigating with medical insurance companies to cover their care. This “financial toxicity” has come to be regarded as a side effect of cancer treatment.

Patients with hematologic malignancies may be particularly vulnerable to financial toxicity, owing to the nature of their treatment, which often includes bone marrow transplantation, lengthy hospital stays, and prolonged intensive follow-up, as well as potential treatment-related complications, such as graft vs. host disease.

The results from this small study suggest that using an oncology financial navigator could be helpful. But not all cancer patients have access to such a person, explained lead author Jean S. Edward, PhD, RN, associate professor in the college of nursing at the University of Kentucky, Lexington.

“Unfortunately, it’s not as common as we would like, especially in underserved areas with patient and caregiver populations that need it the most,” she said. Dr. Edward is hopeful that the results from this study, even though it is small, might help to boost use of this intervention. “OFN [oncology financial navigation] is not necessarily a cutting-edge program or ‘novel’ intervention, but the lack of programs and limitations in implementing in cancer centers does make it a gap in practice,” Dr. Edward told this news organization.

“There are gaps in evidence on how to incorporate an oncology financial navigator in current workflows and sustainability of positions, but as our study has shown, the return on investment to the health care system and/or financial benefits to patients/caregivers could help cover the cost of implementing such programs,” she said.

The study was published in JCO Oncology Practice.

The intervention used in this study, Coverage and Cost-of-Care Links (CC Links), was designed specifically to address financial toxicity among patients with hematologic cancers.

The study’s primary outcomes were defined as improvements in financial distress as well as in physical and mental quality of life.

A total of 54 patients and 32 caregivers completed the intervention and pre-/postintervention surveys. More than half of participants were women. The average age was 63 years. Less than a quarter of the patients were employed (23%), about one-third had income that was below the federal poverty level, and almost all had insurance. About 59% of the caregivers were employed.

The navigators’ functions included screening for financial toxicity using FACIT-Comprehensive Score for Financial Toxicity (COST) and the National Comprehensive Cancer Network’s Distress Thermometer and Problem List. They also helped patients to estimate cost of care, assessed health insurance coverage, and connected patients/caregivers with disease-specific resources and other external assistance programs, among other things.

Participants had an average of three in-person meetings and five telephone interactions with the financial navigator. The most common concern was in regard to high out-of-pocket costs. The most frequently provided services from the navigator were helping with financial assistance programs and grant applications. Overall, the navigator was able to obtain $124,600 in financial benefits for 48 participants, as well as money for travel ($24,000), urgent needs ($16,000), patient financial assistance ($9,100), and copay assistance grants ($75,500).

With regard to scores on the screening tools, the only significant change from pre- to postintervention was in the psychological response score, or COST. It decreased by an average of 2.30 points (P = .019; Hedges’ g = 0.33). For caregivers, there was a significant improvement in COST (average decrease, 2.97 points; P = .021; g = 0.43), material condition scores (average decrease, 0.63 points; P = .031; g = 0.39), and total financial toxicity scores (average decrease, 0.13 points; P = .041; g = 0.37).

Most of the participants gave the intervention high ratings for acceptability (89%) and appropriateness (88%).

“Standardized screening for financial toxicity in cancer care settings is essential to support early identification of financial needs that serve as barriers to care,” the authors conclude. “Close collaboration and coordination with existing services and workflows are essential for the seamless integration of OFN interventions within health systems and to help facilitate contact and communication with participants.”

The study was supported by the National Cancer Institute; the University of Kentucky’s Markey Cancer Center; the Research Communications Office of the Patient Oriented and Population Science Shared Resource Facilities; Joan Scales, LCSW, and the Psych-Oncology Program at the University of Kentucky Markey Cancer Center; and UK HealthCare’s Patient Financial Services. Dr. Edward has disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

In a small cohort of patients with hematologic cancer and their caregivers, the use of a financial navigator helped secure cost savings of approximately $2,500 per person. This saving was achieved by helping participants to optimize health insurance, identify different types of assistance for out-of-pocket expenses, or apply for disability or family medical leave.

Cancer patients in the United States face complex financial issues in navigating with medical insurance companies to cover their care. This “financial toxicity” has come to be regarded as a side effect of cancer treatment.

Patients with hematologic malignancies may be particularly vulnerable to financial toxicity, owing to the nature of their treatment, which often includes bone marrow transplantation, lengthy hospital stays, and prolonged intensive follow-up, as well as potential treatment-related complications, such as graft vs. host disease.

The results from this small study suggest that using an oncology financial navigator could be helpful. But not all cancer patients have access to such a person, explained lead author Jean S. Edward, PhD, RN, associate professor in the college of nursing at the University of Kentucky, Lexington.

“Unfortunately, it’s not as common as we would like, especially in underserved areas with patient and caregiver populations that need it the most,” she said. Dr. Edward is hopeful that the results from this study, even though it is small, might help to boost use of this intervention. “OFN [oncology financial navigation] is not necessarily a cutting-edge program or ‘novel’ intervention, but the lack of programs and limitations in implementing in cancer centers does make it a gap in practice,” Dr. Edward told this news organization.

“There are gaps in evidence on how to incorporate an oncology financial navigator in current workflows and sustainability of positions, but as our study has shown, the return on investment to the health care system and/or financial benefits to patients/caregivers could help cover the cost of implementing such programs,” she said.

The study was published in JCO Oncology Practice.

The intervention used in this study, Coverage and Cost-of-Care Links (CC Links), was designed specifically to address financial toxicity among patients with hematologic cancers.

The study’s primary outcomes were defined as improvements in financial distress as well as in physical and mental quality of life.

A total of 54 patients and 32 caregivers completed the intervention and pre-/postintervention surveys. More than half of participants were women. The average age was 63 years. Less than a quarter of the patients were employed (23%), about one-third had income that was below the federal poverty level, and almost all had insurance. About 59% of the caregivers were employed.

The navigators’ functions included screening for financial toxicity using FACIT-Comprehensive Score for Financial Toxicity (COST) and the National Comprehensive Cancer Network’s Distress Thermometer and Problem List. They also helped patients to estimate cost of care, assessed health insurance coverage, and connected patients/caregivers with disease-specific resources and other external assistance programs, among other things.

Participants had an average of three in-person meetings and five telephone interactions with the financial navigator. The most common concern was in regard to high out-of-pocket costs. The most frequently provided services from the navigator were helping with financial assistance programs and grant applications. Overall, the navigator was able to obtain $124,600 in financial benefits for 48 participants, as well as money for travel ($24,000), urgent needs ($16,000), patient financial assistance ($9,100), and copay assistance grants ($75,500).

With regard to scores on the screening tools, the only significant change from pre- to postintervention was in the psychological response score, or COST. It decreased by an average of 2.30 points (P = .019; Hedges’ g = 0.33). For caregivers, there was a significant improvement in COST (average decrease, 2.97 points; P = .021; g = 0.43), material condition scores (average decrease, 0.63 points; P = .031; g = 0.39), and total financial toxicity scores (average decrease, 0.13 points; P = .041; g = 0.37).

Most of the participants gave the intervention high ratings for acceptability (89%) and appropriateness (88%).

“Standardized screening for financial toxicity in cancer care settings is essential to support early identification of financial needs that serve as barriers to care,” the authors conclude. “Close collaboration and coordination with existing services and workflows are essential for the seamless integration of OFN interventions within health systems and to help facilitate contact and communication with participants.”

The study was supported by the National Cancer Institute; the University of Kentucky’s Markey Cancer Center; the Research Communications Office of the Patient Oriented and Population Science Shared Resource Facilities; Joan Scales, LCSW, and the Psych-Oncology Program at the University of Kentucky Markey Cancer Center; and UK HealthCare’s Patient Financial Services. Dr. Edward has disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

A version of this article first appeared on Medscape.com.

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

A version of this article first appeared on Medscape.com.

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

A version of this article first appeared on Medscape.com.

The incidence of colorectal cancer (CRC) is rapidly increasing among younger individuals, and the disease is also being diagnosed at more advanced stages in all ages, according to a new report from the American Cancer Society.

Diagnoses in people younger than 55 years doubled from 11% (1 in 10) in 1995 to 20% (1 in 5) in 2019.

In addition, more advanced disease is being diagnosed; the proportion of individuals of all ages presenting with advanced-stage CRC increased from 52% in the mid-2000s to 60% in 2019.

“We know rates are increasing in young people, but it’s alarming to see how rapidly the whole patient population is shifting younger, despite shrinking numbers in the overall population,” said Rebecca Siegel, MPH, senior scientific director of surveillance research at the American Cancer Society and lead author of the report.

“The trend toward more advanced disease in people of all ages is also surprising and should motivate everyone 45 and older to get screened,” she added.

The report was published online in CA: A Cancer Journal for Clinicians.

CRC is the third most commonly diagnosed cancer and the third leading cause of cancer death of both men and women in the United States. It is estimated that there will be 153,020 new cases of CRC in the U.S. in 2023, including 106,970 tumors in the colon and 46,050 in the rectum.

Overall, in 2023, an estimated 153,020 people will be diagnosed with CRC in the U.S., and of those, 52,550 people will die from the disease.

The incidence of CRC rapidly decreased during the 2000s among people aged 50 and older, largely because of an increase in cancer screening with colonoscopy. But progress slowed during the past decade, and now the trends toward declining incidence is largely confined to those aged 65 and older.

The authors point out that more than half of all cases and deaths are associated with modifiable risk factors, including smoking, an unhealthy diet, high alcohol consumption, physical inactivity, and excess body weight. A large proportion of CRC incidence and mortality is preventable through recommended screening, surveillance, and high-quality treatment.

But it remains unclear why rates are rising among younger adults and why there is a trend toward the disase being initially diagnosed at more advanced stages.

“We have to address why the rates in young adults continue to trend in the wrong direction,” said Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society and senior author of the study. “We need to invest more in research to uncover the causes of the rising trends and to discover new treatment for advanced-stage diseases to reduce the morbidity and mortality associated with this disease in this young population, who are raising families and supporting other family members.”

For their report, Ms. Siegel and colleagues used incidence data from 1995 to 2019 from 50 states and the District of Columbia. The data came from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and the National Program of Cancer Registries of the U.S. Centers for Disease Control and Prevention, as provided by the North American Association of Central Cancer Registries. National mortality data through 2020 were provided by the National Center for Health Statistics.

The authors note that while overall, deaths from CRC are continuing to fall, “this progress is tempered by a rapidly changing landscape of disease that foreshadows less favorable trends ahead.”

The incidence rates have increased by 2% per year among people younger than 50 years as well as among those aged 50-54 years while, for the past decade, the rates have declined among those aged 65 and older. Incidence rates have stabilized among persons aged 50-64 years.

Although the majority of diagnoses continue to occur among people aged 65 years and older, 19,550 cases (13%) will occur in those younger than age 50 years, and one-third will be diagnosed in those aged 50-64 years.

Other key findings include the following.

• Declines in incidence and mortality have slowed, from 3% to 4% per year during the 2000s to 1% per year for incidence and 2% per year for mortality during the past decade.
• The incidence rate was 33% higher among men than women from 2015 to 2019, which may reflect differences in risk factors, such as excess body weight, processed meat consumption, and a history of smoking.
• The percentage of patients who present with advanced-stage disease has increased from a low of 52% in the mid-2000s to 60% in 2019 despite an increase in the use of screening.
• Death rates from CRC have risen since around 2005 by 1% annually among those younger than 50 years and by 0.6% in people aged 50-54.
• The report also identified racial/ethnic differences in incidence and mortality: Incidence was highest among Alaska Natives (88.5 per 100,000), American Indians (46.0 per 100,000), and Black persons, compared with White persons (41.7 per 100,000 vs. 35.7 per 100,000). Mortality followed a similar pattern; the highest rates were observed among Alaska Natives (50.5 per 100,000), American Indians (17.5 per 100,000), and Black persons, compared with White persons (17.6 per 100,000 vs. 13.1 per 100,000).
• There was also a shift to left-sided tumors, despite greater efficacy of screening for preventing left-sided lesions. The proportion of CRCs occurring in the rectum has steadily risen from 27% in 1995 to 31% in 2019.

“These highly concerning data illustrate the urgent need to invest in targeted cancer research studies dedicated to understanding and preventing early-onset colorectal cancer,” said Karen E. Knudsen, MBA, PhD, and CEO of the American Cancer Society. “The shift to diagnosis of more advanced disease also underscores the importance of screening and early detection, which saves lives.”

The study was supported by the American Cancer Society.

A version of this article first appeared on Medscape.com.

The incidence of colorectal cancer (CRC) is rapidly increasing among younger individuals, and the disease is also being diagnosed at more advanced stages in all ages, according to a new report from the American Cancer Society.

Diagnoses in people younger than 55 years doubled from 11% (1 in 10) in 1995 to 20% (1 in 5) in 2019.

In addition, more advanced disease is being diagnosed; the proportion of individuals of all ages presenting with advanced-stage CRC increased from 52% in the mid-2000s to 60% in 2019.

“We know rates are increasing in young people, but it’s alarming to see how rapidly the whole patient population is shifting younger, despite shrinking numbers in the overall population,” said Rebecca Siegel, MPH, senior scientific director of surveillance research at the American Cancer Society and lead author of the report.

“The trend toward more advanced disease in people of all ages is also surprising and should motivate everyone 45 and older to get screened,” she added.

The report was published online in CA: A Cancer Journal for Clinicians.

CRC is the third most commonly diagnosed cancer and the third leading cause of cancer death of both men and women in the United States. It is estimated that there will be 153,020 new cases of CRC in the U.S. in 2023, including 106,970 tumors in the colon and 46,050 in the rectum.

Overall, in 2023, an estimated 153,020 people will be diagnosed with CRC in the U.S., and of those, 52,550 people will die from the disease.

The incidence of CRC rapidly decreased during the 2000s among people aged 50 and older, largely because of an increase in cancer screening with colonoscopy. But progress slowed during the past decade, and now the trends toward declining incidence is largely confined to those aged 65 and older.

The authors point out that more than half of all cases and deaths are associated with modifiable risk factors, including smoking, an unhealthy diet, high alcohol consumption, physical inactivity, and excess body weight. A large proportion of CRC incidence and mortality is preventable through recommended screening, surveillance, and high-quality treatment.

But it remains unclear why rates are rising among younger adults and why there is a trend toward the disase being initially diagnosed at more advanced stages.

“We have to address why the rates in young adults continue to trend in the wrong direction,” said Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society and senior author of the study. “We need to invest more in research to uncover the causes of the rising trends and to discover new treatment for advanced-stage diseases to reduce the morbidity and mortality associated with this disease in this young population, who are raising families and supporting other family members.”

For their report, Ms. Siegel and colleagues used incidence data from 1995 to 2019 from 50 states and the District of Columbia. The data came from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and the National Program of Cancer Registries of the U.S. Centers for Disease Control and Prevention, as provided by the North American Association of Central Cancer Registries. National mortality data through 2020 were provided by the National Center for Health Statistics.

The authors note that while overall, deaths from CRC are continuing to fall, “this progress is tempered by a rapidly changing landscape of disease that foreshadows less favorable trends ahead.”

The incidence rates have increased by 2% per year among people younger than 50 years as well as among those aged 50-54 years while, for the past decade, the rates have declined among those aged 65 and older. Incidence rates have stabilized among persons aged 50-64 years.

Although the majority of diagnoses continue to occur among people aged 65 years and older, 19,550 cases (13%) will occur in those younger than age 50 years, and one-third will be diagnosed in those aged 50-64 years.

Other key findings include the following.

• Declines in incidence and mortality have slowed, from 3% to 4% per year during the 2000s to 1% per year for incidence and 2% per year for mortality during the past decade.
• The incidence rate was 33% higher among men than women from 2015 to 2019, which may reflect differences in risk factors, such as excess body weight, processed meat consumption, and a history of smoking.
• The percentage of patients who present with advanced-stage disease has increased from a low of 52% in the mid-2000s to 60% in 2019 despite an increase in the use of screening.
• Death rates from CRC have risen since around 2005 by 1% annually among those younger than 50 years and by 0.6% in people aged 50-54.
• The report also identified racial/ethnic differences in incidence and mortality: Incidence was highest among Alaska Natives (88.5 per 100,000), American Indians (46.0 per 100,000), and Black persons, compared with White persons (41.7 per 100,000 vs. 35.7 per 100,000). Mortality followed a similar pattern; the highest rates were observed among Alaska Natives (50.5 per 100,000), American Indians (17.5 per 100,000), and Black persons, compared with White persons (17.6 per 100,000 vs. 13.1 per 100,000).
• There was also a shift to left-sided tumors, despite greater efficacy of screening for preventing left-sided lesions. The proportion of CRCs occurring in the rectum has steadily risen from 27% in 1995 to 31% in 2019.

“These highly concerning data illustrate the urgent need to invest in targeted cancer research studies dedicated to understanding and preventing early-onset colorectal cancer,” said Karen E. Knudsen, MBA, PhD, and CEO of the American Cancer Society. “The shift to diagnosis of more advanced disease also underscores the importance of screening and early detection, which saves lives.”

The study was supported by the American Cancer Society.

A version of this article first appeared on Medscape.com.

The incidence of colorectal cancer (CRC) is rapidly increasing among younger individuals, and the disease is also being diagnosed at more advanced stages in all ages, according to a new report from the American Cancer Society.

Diagnoses in people younger than 55 years doubled from 11% (1 in 10) in 1995 to 20% (1 in 5) in 2019.

In addition, more advanced disease is being diagnosed; the proportion of individuals of all ages presenting with advanced-stage CRC increased from 52% in the mid-2000s to 60% in 2019.

“We know rates are increasing in young people, but it’s alarming to see how rapidly the whole patient population is shifting younger, despite shrinking numbers in the overall population,” said Rebecca Siegel, MPH, senior scientific director of surveillance research at the American Cancer Society and lead author of the report.

“The trend toward more advanced disease in people of all ages is also surprising and should motivate everyone 45 and older to get screened,” she added.

The report was published online in CA: A Cancer Journal for Clinicians.

CRC is the third most commonly diagnosed cancer and the third leading cause of cancer death of both men and women in the United States. It is estimated that there will be 153,020 new cases of CRC in the U.S. in 2023, including 106,970 tumors in the colon and 46,050 in the rectum.

Overall, in 2023, an estimated 153,020 people will be diagnosed with CRC in the U.S., and of those, 52,550 people will die from the disease.

The incidence of CRC rapidly decreased during the 2000s among people aged 50 and older, largely because of an increase in cancer screening with colonoscopy. But progress slowed during the past decade, and now the trends toward declining incidence is largely confined to those aged 65 and older.

The authors point out that more than half of all cases and deaths are associated with modifiable risk factors, including smoking, an unhealthy diet, high alcohol consumption, physical inactivity, and excess body weight. A large proportion of CRC incidence and mortality is preventable through recommended screening, surveillance, and high-quality treatment.

But it remains unclear why rates are rising among younger adults and why there is a trend toward the disase being initially diagnosed at more advanced stages.

“We have to address why the rates in young adults continue to trend in the wrong direction,” said Ahmedin Jemal, DVM, PhD, senior vice president of surveillance and health equity science at the American Cancer Society and senior author of the study. “We need to invest more in research to uncover the causes of the rising trends and to discover new treatment for advanced-stage diseases to reduce the morbidity and mortality associated with this disease in this young population, who are raising families and supporting other family members.”

For their report, Ms. Siegel and colleagues used incidence data from 1995 to 2019 from 50 states and the District of Columbia. The data came from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and the National Program of Cancer Registries of the U.S. Centers for Disease Control and Prevention, as provided by the North American Association of Central Cancer Registries. National mortality data through 2020 were provided by the National Center for Health Statistics.

The authors note that while overall, deaths from CRC are continuing to fall, “this progress is tempered by a rapidly changing landscape of disease that foreshadows less favorable trends ahead.”

The incidence rates have increased by 2% per year among people younger than 50 years as well as among those aged 50-54 years while, for the past decade, the rates have declined among those aged 65 and older. Incidence rates have stabilized among persons aged 50-64 years.

Although the majority of diagnoses continue to occur among people aged 65 years and older, 19,550 cases (13%) will occur in those younger than age 50 years, and one-third will be diagnosed in those aged 50-64 years.

Other key findings include the following.

• Declines in incidence and mortality have slowed, from 3% to 4% per year during the 2000s to 1% per year for incidence and 2% per year for mortality during the past decade.
• The incidence rate was 33% higher among men than women from 2015 to 2019, which may reflect differences in risk factors, such as excess body weight, processed meat consumption, and a history of smoking.
• The percentage of patients who present with advanced-stage disease has increased from a low of 52% in the mid-2000s to 60% in 2019 despite an increase in the use of screening.
• Death rates from CRC have risen since around 2005 by 1% annually among those younger than 50 years and by 0.6% in people aged 50-54.
• The report also identified racial/ethnic differences in incidence and mortality: Incidence was highest among Alaska Natives (88.5 per 100,000), American Indians (46.0 per 100,000), and Black persons, compared with White persons (41.7 per 100,000 vs. 35.7 per 100,000). Mortality followed a similar pattern; the highest rates were observed among Alaska Natives (50.5 per 100,000), American Indians (17.5 per 100,000), and Black persons, compared with White persons (17.6 per 100,000 vs. 13.1 per 100,000).
• There was also a shift to left-sided tumors, despite greater efficacy of screening for preventing left-sided lesions. The proportion of CRCs occurring in the rectum has steadily risen from 27% in 1995 to 31% in 2019.

“These highly concerning data illustrate the urgent need to invest in targeted cancer research studies dedicated to understanding and preventing early-onset colorectal cancer,” said Karen E. Knudsen, MBA, PhD, and CEO of the American Cancer Society. “The shift to diagnosis of more advanced disease also underscores the importance of screening and early detection, which saves lives.”

The study was supported by the American Cancer Society.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – For patients with prostate cancer who have unfavorable features and a detectable PSA following a radical prostatectomy, the standard of care is treatment with 6 months of a gonadotropin-releasing hormone (GnRH) agonist with salvage radiation therapy (SRT), as established by the GETUG-AFU 16 trial.

A new trial, dubbed FORMULA-509, explored whether outcomes could be improved by intensifying the drug treatment by adding 6 months of abiraterone acetate plus prednisone as well as apalutamide on top of the GnRH agonist alongside the salvage radiotherapy.

This approach did not provide a significant improvement in progression-free survival (PFS) or metastasis-free survival (MFS) in the overall study population.

However, the combination did significantly improve PFS and MFS in a subset of men with PSA levels greater than 0.5 ng/mL.

“Although this primary analysis did not meet the prespecified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy plus 6 months of ADT [androgen deprivation therapy] may improve progression-free survival and metastasis-free survival,” said lead author Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston, and professor of radiation oncology at Harvard Medical School.

“This may be particularly evident in the subgroup of patients with PSA greater that 0.5 ng/mL where a preplanned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival,” he said. “Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy.”

The study results were presented at the ASCO Genitourinary Cancers Symposium.
 

Benefit in subset

The FORMULA-509 trial included 305 patients with PSA ≥ 0.1 ng/mL who had undergone a radical prostatectomy, and who had one or more unfavorable risk features (Gleason 8-10 disease, PSA > 0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time < 10 months, negative margins, persistent PSA, gross local/regional disease).

“This was a pretty high-risk population,” Dr. Nguyen emphasized, as 35% had Gleason score of 9, about a third (31%) a PSA >0.5, and 29% were pathologic node positive.

All patients received salvage radiotherapy plus 6 months of GnRH agonist (bicalutamide 50 mg), and half were randomly assigned to also receive abiraterone acetate/prednisone 1,000 mg/5 mg + apalutamide 240 mg daily.

At a median follow-up of 34 months, the 3-year PFS rate was 74.9% in the AAP-apalutamide arm vs. 68.5% for the control group (hazard ratio [HR], 0.71; P = .06), and the 3-year MFS rate was 90.6% vs. 87.2%, respectively (HR, 0.57; P = .05).

In the subset of patients with a PSA greater than 0.5 ng/mL, the 3-year PFS and MFS rates were significantly higher with in the AAP-apalutamide group: the 3-year PFS rate was 67.2% vs. 46.8% (HR, 0.50; P = .03), and the 3-year MFS rate was 84.3% vs. 66.1% (HR, 0.32; P = .02).

Adverse events were consistent with the known safety profiles of the agents being studied, Dr. Nguyen noted. The most common toxicities for AAP-apalutamide vs. controls were hypertension (21.8% vs. 13.3%), maculopapular rash (11.5% vs. 0.6%), diarrhea (8.5% vs. 4.8%), and fatigue (7.9% vs. 6.1%).

Dr. Nguyen noted that even though “we’re not supposed to compare clinical trials,” the results of this study appeared to compare favorably with those of another trial, RADICALS-HD, which was presented at the 2022 European Society of Medical Oncology Congress. That study showed that in patients undergoing postoperative radiation therapy, 24 months of ADT was superior to 6 months of ADT in improving both time to salvage ADT and MFS.

However, Dr. Nguyen emphasized that it would have to be formally tested, to see if “FORMULA-509 is performing in the ballpark of what 24 months of ADT would do.

“And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark,” he said. “So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months.”

He added that this concept would be formally tested in the upcoming PROSTATE IQ study.
 

Strong evidence, standardization needed

In a discussion of the paper, Tyler Seibert, MD, PhD, of the University of California San Diego, said that “escalation by 24 months has the strongest evidence today, specifically from the RADICALS-HD trial, with more than 1,500 men with 10 years of  follow-up and a clear statistically significant result.

“Intensification for 6 months is a very compelling concept, as most patients are not getting 2 years of androgen deprivation therapy at this point post prostatectomy,” he continued. “While we await the long term follow-up of this study and the pending PROSTATE IQ trial, and if only 6 months of therapy is acceptable or feasible, the FORMULA-509 [trial] provides convincing evidence that select patients would benefit from intensification with AAP and apalutamide.”

Another expert weighed in on the data. Approached by this news organization for an independent comment, Jeff M. Michalski, MD, MBA, professor of radiation oncology at Washington University, St Louis, and president of the American Society of Radiation Oncology, noted a few issues in the study.

He said that standards had changed since this study was first approved and had begun accrual several years ago. “In context of today’s era, the current standard is to do a PET scan if patients have a chemical failure after surgery,” he said. “The PSA levels of patients who were treated [in this trial] were very high, and many patients do not want to wait until they reach that level.”

Dr. Michalski also pointed out the number of patients getting radiation was less than the number who had node-positive disease. “This shows that patients had received suboptimal therapy late in the disease,” he said.

Overall, most patients in the study did not receive lymph node radiation, even though they had high-risk features. “A recent study of almost 1,800 patients that was published in The Lancet found that there is a benefit to pelvic lymph node radiation,” he said. “Because it wasn’t mandated, most of the patients did not receive pelvic lymph node radiation, which we now understand offers some benefit.”

The reasons for not giving pelvic radiation to these men is unclear. “Treatment was left at the discretion of the physician and this could create bias,” Dr. Michalski said. “It could drive one arm more than another.”

The study also wasn’t controlled for pelvic radiation. “Most of the nodal positive patients received it, but the other patients were undertreated,” he noted.

Dr. Michalski added that he hopes that in the forthcoming PROSTATE IQ study, lymph node radiation and imaging are standardized.

The trial was supported by Janssen Oncology. Dr. Nguyen disclosed relationships with, and/or support from, Volatilyx, Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences, Astellas Pharma, and Janssen. Dr. Seibert disclosed relationships with, and/or support from, CorTechs Labs, Varian Medical Systems, and GE Healthcare.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – For patients with prostate cancer who have unfavorable features and a detectable PSA following a radical prostatectomy, the standard of care is treatment with 6 months of a gonadotropin-releasing hormone (GnRH) agonist with salvage radiation therapy (SRT), as established by the GETUG-AFU 16 trial.

A new trial, dubbed FORMULA-509, explored whether outcomes could be improved by intensifying the drug treatment by adding 6 months of abiraterone acetate plus prednisone as well as apalutamide on top of the GnRH agonist alongside the salvage radiotherapy.

This approach did not provide a significant improvement in progression-free survival (PFS) or metastasis-free survival (MFS) in the overall study population.

However, the combination did significantly improve PFS and MFS in a subset of men with PSA levels greater than 0.5 ng/mL.

“Although this primary analysis did not meet the prespecified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy plus 6 months of ADT [androgen deprivation therapy] may improve progression-free survival and metastasis-free survival,” said lead author Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston, and professor of radiation oncology at Harvard Medical School.

“This may be particularly evident in the subgroup of patients with PSA greater that 0.5 ng/mL where a preplanned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival,” he said. “Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy.”

The study results were presented at the ASCO Genitourinary Cancers Symposium.
 

Benefit in subset

The FORMULA-509 trial included 305 patients with PSA ≥ 0.1 ng/mL who had undergone a radical prostatectomy, and who had one or more unfavorable risk features (Gleason 8-10 disease, PSA > 0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time < 10 months, negative margins, persistent PSA, gross local/regional disease).

“This was a pretty high-risk population,” Dr. Nguyen emphasized, as 35% had Gleason score of 9, about a third (31%) a PSA >0.5, and 29% were pathologic node positive.

All patients received salvage radiotherapy plus 6 months of GnRH agonist (bicalutamide 50 mg), and half were randomly assigned to also receive abiraterone acetate/prednisone 1,000 mg/5 mg + apalutamide 240 mg daily.

At a median follow-up of 34 months, the 3-year PFS rate was 74.9% in the AAP-apalutamide arm vs. 68.5% for the control group (hazard ratio [HR], 0.71; P = .06), and the 3-year MFS rate was 90.6% vs. 87.2%, respectively (HR, 0.57; P = .05).

In the subset of patients with a PSA greater than 0.5 ng/mL, the 3-year PFS and MFS rates were significantly higher with in the AAP-apalutamide group: the 3-year PFS rate was 67.2% vs. 46.8% (HR, 0.50; P = .03), and the 3-year MFS rate was 84.3% vs. 66.1% (HR, 0.32; P = .02).

Adverse events were consistent with the known safety profiles of the agents being studied, Dr. Nguyen noted. The most common toxicities for AAP-apalutamide vs. controls were hypertension (21.8% vs. 13.3%), maculopapular rash (11.5% vs. 0.6%), diarrhea (8.5% vs. 4.8%), and fatigue (7.9% vs. 6.1%).

Dr. Nguyen noted that even though “we’re not supposed to compare clinical trials,” the results of this study appeared to compare favorably with those of another trial, RADICALS-HD, which was presented at the 2022 European Society of Medical Oncology Congress. That study showed that in patients undergoing postoperative radiation therapy, 24 months of ADT was superior to 6 months of ADT in improving both time to salvage ADT and MFS.

However, Dr. Nguyen emphasized that it would have to be formally tested, to see if “FORMULA-509 is performing in the ballpark of what 24 months of ADT would do.

“And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark,” he said. “So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months.”

He added that this concept would be formally tested in the upcoming PROSTATE IQ study.
 

Strong evidence, standardization needed

In a discussion of the paper, Tyler Seibert, MD, PhD, of the University of California San Diego, said that “escalation by 24 months has the strongest evidence today, specifically from the RADICALS-HD trial, with more than 1,500 men with 10 years of  follow-up and a clear statistically significant result.

“Intensification for 6 months is a very compelling concept, as most patients are not getting 2 years of androgen deprivation therapy at this point post prostatectomy,” he continued. “While we await the long term follow-up of this study and the pending PROSTATE IQ trial, and if only 6 months of therapy is acceptable or feasible, the FORMULA-509 [trial] provides convincing evidence that select patients would benefit from intensification with AAP and apalutamide.”

Another expert weighed in on the data. Approached by this news organization for an independent comment, Jeff M. Michalski, MD, MBA, professor of radiation oncology at Washington University, St Louis, and president of the American Society of Radiation Oncology, noted a few issues in the study.

He said that standards had changed since this study was first approved and had begun accrual several years ago. “In context of today’s era, the current standard is to do a PET scan if patients have a chemical failure after surgery,” he said. “The PSA levels of patients who were treated [in this trial] were very high, and many patients do not want to wait until they reach that level.”

Dr. Michalski also pointed out the number of patients getting radiation was less than the number who had node-positive disease. “This shows that patients had received suboptimal therapy late in the disease,” he said.

Overall, most patients in the study did not receive lymph node radiation, even though they had high-risk features. “A recent study of almost 1,800 patients that was published in The Lancet found that there is a benefit to pelvic lymph node radiation,” he said. “Because it wasn’t mandated, most of the patients did not receive pelvic lymph node radiation, which we now understand offers some benefit.”

The reasons for not giving pelvic radiation to these men is unclear. “Treatment was left at the discretion of the physician and this could create bias,” Dr. Michalski said. “It could drive one arm more than another.”

The study also wasn’t controlled for pelvic radiation. “Most of the nodal positive patients received it, but the other patients were undertreated,” he noted.

Dr. Michalski added that he hopes that in the forthcoming PROSTATE IQ study, lymph node radiation and imaging are standardized.

The trial was supported by Janssen Oncology. Dr. Nguyen disclosed relationships with, and/or support from, Volatilyx, Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences, Astellas Pharma, and Janssen. Dr. Seibert disclosed relationships with, and/or support from, CorTechs Labs, Varian Medical Systems, and GE Healthcare.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – For patients with prostate cancer who have unfavorable features and a detectable PSA following a radical prostatectomy, the standard of care is treatment with 6 months of a gonadotropin-releasing hormone (GnRH) agonist with salvage radiation therapy (SRT), as established by the GETUG-AFU 16 trial.

A new trial, dubbed FORMULA-509, explored whether outcomes could be improved by intensifying the drug treatment by adding 6 months of abiraterone acetate plus prednisone as well as apalutamide on top of the GnRH agonist alongside the salvage radiotherapy.

This approach did not provide a significant improvement in progression-free survival (PFS) or metastasis-free survival (MFS) in the overall study population.

However, the combination did significantly improve PFS and MFS in a subset of men with PSA levels greater than 0.5 ng/mL.

“Although this primary analysis did not meet the prespecified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy plus 6 months of ADT [androgen deprivation therapy] may improve progression-free survival and metastasis-free survival,” said lead author Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston, and professor of radiation oncology at Harvard Medical School.

“This may be particularly evident in the subgroup of patients with PSA greater that 0.5 ng/mL where a preplanned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival,” he said. “Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy.”

The study results were presented at the ASCO Genitourinary Cancers Symposium.
 

Benefit in subset

The FORMULA-509 trial included 305 patients with PSA ≥ 0.1 ng/mL who had undergone a radical prostatectomy, and who had one or more unfavorable risk features (Gleason 8-10 disease, PSA > 0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time < 10 months, negative margins, persistent PSA, gross local/regional disease).

“This was a pretty high-risk population,” Dr. Nguyen emphasized, as 35% had Gleason score of 9, about a third (31%) a PSA >0.5, and 29% were pathologic node positive.

All patients received salvage radiotherapy plus 6 months of GnRH agonist (bicalutamide 50 mg), and half were randomly assigned to also receive abiraterone acetate/prednisone 1,000 mg/5 mg + apalutamide 240 mg daily.

At a median follow-up of 34 months, the 3-year PFS rate was 74.9% in the AAP-apalutamide arm vs. 68.5% for the control group (hazard ratio [HR], 0.71; P = .06), and the 3-year MFS rate was 90.6% vs. 87.2%, respectively (HR, 0.57; P = .05).

In the subset of patients with a PSA greater than 0.5 ng/mL, the 3-year PFS and MFS rates were significantly higher with in the AAP-apalutamide group: the 3-year PFS rate was 67.2% vs. 46.8% (HR, 0.50; P = .03), and the 3-year MFS rate was 84.3% vs. 66.1% (HR, 0.32; P = .02).

Adverse events were consistent with the known safety profiles of the agents being studied, Dr. Nguyen noted. The most common toxicities for AAP-apalutamide vs. controls were hypertension (21.8% vs. 13.3%), maculopapular rash (11.5% vs. 0.6%), diarrhea (8.5% vs. 4.8%), and fatigue (7.9% vs. 6.1%).

Dr. Nguyen noted that even though “we’re not supposed to compare clinical trials,” the results of this study appeared to compare favorably with those of another trial, RADICALS-HD, which was presented at the 2022 European Society of Medical Oncology Congress. That study showed that in patients undergoing postoperative radiation therapy, 24 months of ADT was superior to 6 months of ADT in improving both time to salvage ADT and MFS.

However, Dr. Nguyen emphasized that it would have to be formally tested, to see if “FORMULA-509 is performing in the ballpark of what 24 months of ADT would do.

“And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark,” he said. “So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months.”

He added that this concept would be formally tested in the upcoming PROSTATE IQ study.
 

Strong evidence, standardization needed

In a discussion of the paper, Tyler Seibert, MD, PhD, of the University of California San Diego, said that “escalation by 24 months has the strongest evidence today, specifically from the RADICALS-HD trial, with more than 1,500 men with 10 years of  follow-up and a clear statistically significant result.

“Intensification for 6 months is a very compelling concept, as most patients are not getting 2 years of androgen deprivation therapy at this point post prostatectomy,” he continued. “While we await the long term follow-up of this study and the pending PROSTATE IQ trial, and if only 6 months of therapy is acceptable or feasible, the FORMULA-509 [trial] provides convincing evidence that select patients would benefit from intensification with AAP and apalutamide.”

Another expert weighed in on the data. Approached by this news organization for an independent comment, Jeff M. Michalski, MD, MBA, professor of radiation oncology at Washington University, St Louis, and president of the American Society of Radiation Oncology, noted a few issues in the study.

He said that standards had changed since this study was first approved and had begun accrual several years ago. “In context of today’s era, the current standard is to do a PET scan if patients have a chemical failure after surgery,” he said. “The PSA levels of patients who were treated [in this trial] were very high, and many patients do not want to wait until they reach that level.”

Dr. Michalski also pointed out the number of patients getting radiation was less than the number who had node-positive disease. “This shows that patients had received suboptimal therapy late in the disease,” he said.

Overall, most patients in the study did not receive lymph node radiation, even though they had high-risk features. “A recent study of almost 1,800 patients that was published in The Lancet found that there is a benefit to pelvic lymph node radiation,” he said. “Because it wasn’t mandated, most of the patients did not receive pelvic lymph node radiation, which we now understand offers some benefit.”

The reasons for not giving pelvic radiation to these men is unclear. “Treatment was left at the discretion of the physician and this could create bias,” Dr. Michalski said. “It could drive one arm more than another.”

The study also wasn’t controlled for pelvic radiation. “Most of the nodal positive patients received it, but the other patients were undertreated,” he noted.

Dr. Michalski added that he hopes that in the forthcoming PROSTATE IQ study, lymph node radiation and imaging are standardized.

The trial was supported by Janssen Oncology. Dr. Nguyen disclosed relationships with, and/or support from, Volatilyx, Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences, Astellas Pharma, and Janssen. Dr. Seibert disclosed relationships with, and/or support from, CorTechs Labs, Varian Medical Systems, and GE Healthcare.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Adding the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib (Talzenna, Pfizer) to treatment with the androgen pathway inhibitor enzalutamide (Xtandi, Astellas, Pfizer) significantly improved progression-free survival (PFS) in comparison with enzalutamide alone for patients with metastatic, castration-resistant prostate cancer (mCRPC) in the TALAPRO-2 trial.

As determined on the basis of imaging, PFS was 37% better for talazoparib plus enzalutamide than for enzalutamide monotherapy. Combination therapy proved superior regardless of homologous recombination repair (HRR) pathway status, noted the authors.

“Not only did the combination therapy delay disease progression, it also significantly delayed progression of PSA [prostate-specific antigen] readings and the time until chemotherapy was needed compared to the control group,” said lead study author Neeraj Agarwal, MD, professor of medicine and director of the genitourinary oncology program at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

“This is important because advanced prostate cancer can be associated with pain, fractures, suffering, and death. The current standard of care treatments were approved almost a decade ago, leaving a huge, unmet need for novel drugs in this setting,” he said.

The new results could pave the way for a prostate cancer indication for talazoparib; the company has said that it will submit these data to regulatory authorities. At present, the drug is approved only for use in BRCA+ breast cancer, an indication that was approved in 2018.

The findings were presented at the 2023 ASCO Genitourinary Cancers Symposium.

Overall, talazoparib plus enzalutamide resulted in a statistically significant and clinically meaningful improvement in PFS over placebo plus enzalutamide. “Results from the primary analysis of the TALAPRO-2 trial support the use of talazoparib plus enzalutamide as a first-line treatment in patients with mCRPC regardless of HRR gene alteration status,” Dr. Agarwal and colleagues concluded.

However, one expert disagreed with the authors’ conclusion regarding HHR pathway status. On the basis of imaging, PFS was 54% better in HHR-deficient patients in the combination therapy group. It was 30% better for patients with HHR-nondeficient tumors or tumors without known HHR status based on imaging and 34% better based on tumor tissue testing.

“There was a huge magnitude in benefit based on HHR, and I think HRR status matters,” commented Elena Castro, MD, PhD, Instituto de Investigación Biomédica de Málaga (Spain), who served as the invited discussant.

“We need to understand the benefit of ARPi [androgen receptor pathway inhibition] and PARP inhibitors better,” she said. “The balance between side effects and benefit depends on HRR status.”

Dr. Castro also noted that the treatment landscape has changed. ARPi is now a standard of care for metastatic prostate cancer, both for hormone-sensitive and castration-resistant disease. “So the question is, does the addition of a PARP inhibitor induce responses after progression to an ARPi in HHR-nondeficient tumors?”
 

Study details

In the TALAPRO-2 trial, Dr. Agarwal and colleagues randomly assigned 805 patients to receive either talazoparib 0.5 mg or placebo. All patients in the cohort received enzalutamide 160 mg daily.

Participants had mCRPC and were unselected for genetic alterations in DNA damage repair pathways directly or indirectly involved with HRR. They were aged 36-91 years (median age, 71). The cohort was enrolled from 25 countries, including the United States, Canada, Europe, South America, and countries in the Asia-Pacific region.

The men were stratified on the basis of prior use of abiraterone or docetaxel for castration-sensitive prostate cancer and HRR gene alteration status. The study’s primary endpoint was imaging-based PFS (ibPFS) by blinded independent central review (BICR).

Overall, median ibPFS by BICR was significantly improved in the combination group in comparison with the patients who received placebo; it was not reached versus 21.9 months (hazard ratio, 0.63; P < .001). It was also significantly improved among the HRR-deficient subgroup (HR, 0.46; P < .001) as well as in the HRR-nondeficient or unknown (HR, 0.70; P = .004) and HRR-nondeficient patients by tumor tissue testing (HR, 0.66; P = .009).

Talazoparib plus enzalutamide was also favored with regard to other endpoints. Dr. Agarwal noted that, while overall survival data are as yet immature, objective response rates, PSA response of at least 50%, and time to PSA progression and use of subsequent cytotoxic chemotherapy and antineoplastic therapy significantly favored the talazoparib group.

The objective response rate was 61.7% versus 43.9% (P = .005), with 37.5% versus 18.2% complete responses.

“The higher rates of complete response suggest a cooperative effect of talazoparib plus enzalutamide treatment,” he explained.
 

High rate of adverse events

The rate of treatment-emergent adverse events was higher among patients who received talazoparib plus enzalutamide; 71.9% of the patients who received talazoparib plus enzalutamide experienced grade 3-4 TEAEs versus 40.6%. The most common grade 3 or greater TEAEs in the talazoparib group were anemia, low neutrophil counts, and low platelet counts. Hypertension, anemia, and fatigue were the most common in the placebo group. Talazoparib was discontinued in 19.1% of patients because of TEAEs. Enzalutamide was discontinued in 10.8% of patients in the combination group versus 11.0% in the placebo group.

Dr. Agarwal pointed out that there were TEAEs of special interest for talazoparib. “Myelodysplastic syndrome was reported in one patient during the safety reporting period, and acute myeloid leukemia was reported in one patient during the follow-up period,” he said.

Additionally, pulmonary embolism was reported in 10 (2.5%) patients (grade 3 in 9 patients) in the talazoparib arm and in 3 (0.7%) patients (all grade 3) in the placebo arm.
 

Results less relevant

Commenting on the study, Matthew Zibelman, MD, associate professor, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that these results represent an “intriguing finding for men with mCRPC, particularly in conjunction with the previously reported PROPEL study results.

“However, given that many patients receive an androgen receptor inhibitor now for metastatic castration-sensitive prostate cancer, these results are less relevant to current practice,” Dr. Zibelman said.

“Demonstration of an overall survival benefit of the combination would be optimal to change standard of care vs potential sequential therapy.”

The study was sponsored by Pfizer, manufacturer of enzalutamide and talazoparib. Dr. Agarwal has relationships with numerous pharmaceutical companies. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis and Pfizer, and Roche. Dr. Zibelman has relationships with Bristol-Myers Squibb, Exelixis, Pfizer, Jannsen, EMD Serono, and Blue Earth.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Adding the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib (Talzenna, Pfizer) to treatment with the androgen pathway inhibitor enzalutamide (Xtandi, Astellas, Pfizer) significantly improved progression-free survival (PFS) in comparison with enzalutamide alone for patients with metastatic, castration-resistant prostate cancer (mCRPC) in the TALAPRO-2 trial.

As determined on the basis of imaging, PFS was 37% better for talazoparib plus enzalutamide than for enzalutamide monotherapy. Combination therapy proved superior regardless of homologous recombination repair (HRR) pathway status, noted the authors.

“Not only did the combination therapy delay disease progression, it also significantly delayed progression of PSA [prostate-specific antigen] readings and the time until chemotherapy was needed compared to the control group,” said lead study author Neeraj Agarwal, MD, professor of medicine and director of the genitourinary oncology program at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

“This is important because advanced prostate cancer can be associated with pain, fractures, suffering, and death. The current standard of care treatments were approved almost a decade ago, leaving a huge, unmet need for novel drugs in this setting,” he said.

The new results could pave the way for a prostate cancer indication for talazoparib; the company has said that it will submit these data to regulatory authorities. At present, the drug is approved only for use in BRCA+ breast cancer, an indication that was approved in 2018.

The findings were presented at the 2023 ASCO Genitourinary Cancers Symposium.

Overall, talazoparib plus enzalutamide resulted in a statistically significant and clinically meaningful improvement in PFS over placebo plus enzalutamide. “Results from the primary analysis of the TALAPRO-2 trial support the use of talazoparib plus enzalutamide as a first-line treatment in patients with mCRPC regardless of HRR gene alteration status,” Dr. Agarwal and colleagues concluded.

However, one expert disagreed with the authors’ conclusion regarding HHR pathway status. On the basis of imaging, PFS was 54% better in HHR-deficient patients in the combination therapy group. It was 30% better for patients with HHR-nondeficient tumors or tumors without known HHR status based on imaging and 34% better based on tumor tissue testing.

“There was a huge magnitude in benefit based on HHR, and I think HRR status matters,” commented Elena Castro, MD, PhD, Instituto de Investigación Biomédica de Málaga (Spain), who served as the invited discussant.

“We need to understand the benefit of ARPi [androgen receptor pathway inhibition] and PARP inhibitors better,” she said. “The balance between side effects and benefit depends on HRR status.”

Dr. Castro also noted that the treatment landscape has changed. ARPi is now a standard of care for metastatic prostate cancer, both for hormone-sensitive and castration-resistant disease. “So the question is, does the addition of a PARP inhibitor induce responses after progression to an ARPi in HHR-nondeficient tumors?”
 

Study details

In the TALAPRO-2 trial, Dr. Agarwal and colleagues randomly assigned 805 patients to receive either talazoparib 0.5 mg or placebo. All patients in the cohort received enzalutamide 160 mg daily.

Participants had mCRPC and were unselected for genetic alterations in DNA damage repair pathways directly or indirectly involved with HRR. They were aged 36-91 years (median age, 71). The cohort was enrolled from 25 countries, including the United States, Canada, Europe, South America, and countries in the Asia-Pacific region.

The men were stratified on the basis of prior use of abiraterone or docetaxel for castration-sensitive prostate cancer and HRR gene alteration status. The study’s primary endpoint was imaging-based PFS (ibPFS) by blinded independent central review (BICR).

Overall, median ibPFS by BICR was significantly improved in the combination group in comparison with the patients who received placebo; it was not reached versus 21.9 months (hazard ratio, 0.63; P < .001). It was also significantly improved among the HRR-deficient subgroup (HR, 0.46; P < .001) as well as in the HRR-nondeficient or unknown (HR, 0.70; P = .004) and HRR-nondeficient patients by tumor tissue testing (HR, 0.66; P = .009).

Talazoparib plus enzalutamide was also favored with regard to other endpoints. Dr. Agarwal noted that, while overall survival data are as yet immature, objective response rates, PSA response of at least 50%, and time to PSA progression and use of subsequent cytotoxic chemotherapy and antineoplastic therapy significantly favored the talazoparib group.

The objective response rate was 61.7% versus 43.9% (P = .005), with 37.5% versus 18.2% complete responses.

“The higher rates of complete response suggest a cooperative effect of talazoparib plus enzalutamide treatment,” he explained.
 

High rate of adverse events

The rate of treatment-emergent adverse events was higher among patients who received talazoparib plus enzalutamide; 71.9% of the patients who received talazoparib plus enzalutamide experienced grade 3-4 TEAEs versus 40.6%. The most common grade 3 or greater TEAEs in the talazoparib group were anemia, low neutrophil counts, and low platelet counts. Hypertension, anemia, and fatigue were the most common in the placebo group. Talazoparib was discontinued in 19.1% of patients because of TEAEs. Enzalutamide was discontinued in 10.8% of patients in the combination group versus 11.0% in the placebo group.

Dr. Agarwal pointed out that there were TEAEs of special interest for talazoparib. “Myelodysplastic syndrome was reported in one patient during the safety reporting period, and acute myeloid leukemia was reported in one patient during the follow-up period,” he said.

Additionally, pulmonary embolism was reported in 10 (2.5%) patients (grade 3 in 9 patients) in the talazoparib arm and in 3 (0.7%) patients (all grade 3) in the placebo arm.
 

Results less relevant

Commenting on the study, Matthew Zibelman, MD, associate professor, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that these results represent an “intriguing finding for men with mCRPC, particularly in conjunction with the previously reported PROPEL study results.

“However, given that many patients receive an androgen receptor inhibitor now for metastatic castration-sensitive prostate cancer, these results are less relevant to current practice,” Dr. Zibelman said.

“Demonstration of an overall survival benefit of the combination would be optimal to change standard of care vs potential sequential therapy.”

The study was sponsored by Pfizer, manufacturer of enzalutamide and talazoparib. Dr. Agarwal has relationships with numerous pharmaceutical companies. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis and Pfizer, and Roche. Dr. Zibelman has relationships with Bristol-Myers Squibb, Exelixis, Pfizer, Jannsen, EMD Serono, and Blue Earth.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – Adding the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib (Talzenna, Pfizer) to treatment with the androgen pathway inhibitor enzalutamide (Xtandi, Astellas, Pfizer) significantly improved progression-free survival (PFS) in comparison with enzalutamide alone for patients with metastatic, castration-resistant prostate cancer (mCRPC) in the TALAPRO-2 trial.

As determined on the basis of imaging, PFS was 37% better for talazoparib plus enzalutamide than for enzalutamide monotherapy. Combination therapy proved superior regardless of homologous recombination repair (HRR) pathway status, noted the authors.

“Not only did the combination therapy delay disease progression, it also significantly delayed progression of PSA [prostate-specific antigen] readings and the time until chemotherapy was needed compared to the control group,” said lead study author Neeraj Agarwal, MD, professor of medicine and director of the genitourinary oncology program at the Huntsman Cancer Institute, University of Utah, Salt Lake City.

“This is important because advanced prostate cancer can be associated with pain, fractures, suffering, and death. The current standard of care treatments were approved almost a decade ago, leaving a huge, unmet need for novel drugs in this setting,” he said.

The new results could pave the way for a prostate cancer indication for talazoparib; the company has said that it will submit these data to regulatory authorities. At present, the drug is approved only for use in BRCA+ breast cancer, an indication that was approved in 2018.

The findings were presented at the 2023 ASCO Genitourinary Cancers Symposium.

Overall, talazoparib plus enzalutamide resulted in a statistically significant and clinically meaningful improvement in PFS over placebo plus enzalutamide. “Results from the primary analysis of the TALAPRO-2 trial support the use of talazoparib plus enzalutamide as a first-line treatment in patients with mCRPC regardless of HRR gene alteration status,” Dr. Agarwal and colleagues concluded.

However, one expert disagreed with the authors’ conclusion regarding HHR pathway status. On the basis of imaging, PFS was 54% better in HHR-deficient patients in the combination therapy group. It was 30% better for patients with HHR-nondeficient tumors or tumors without known HHR status based on imaging and 34% better based on tumor tissue testing.

“There was a huge magnitude in benefit based on HHR, and I think HRR status matters,” commented Elena Castro, MD, PhD, Instituto de Investigación Biomédica de Málaga (Spain), who served as the invited discussant.

“We need to understand the benefit of ARPi [androgen receptor pathway inhibition] and PARP inhibitors better,” she said. “The balance between side effects and benefit depends on HRR status.”

Dr. Castro also noted that the treatment landscape has changed. ARPi is now a standard of care for metastatic prostate cancer, both for hormone-sensitive and castration-resistant disease. “So the question is, does the addition of a PARP inhibitor induce responses after progression to an ARPi in HHR-nondeficient tumors?”
 

Study details

In the TALAPRO-2 trial, Dr. Agarwal and colleagues randomly assigned 805 patients to receive either talazoparib 0.5 mg or placebo. All patients in the cohort received enzalutamide 160 mg daily.

Participants had mCRPC and were unselected for genetic alterations in DNA damage repair pathways directly or indirectly involved with HRR. They were aged 36-91 years (median age, 71). The cohort was enrolled from 25 countries, including the United States, Canada, Europe, South America, and countries in the Asia-Pacific region.

The men were stratified on the basis of prior use of abiraterone or docetaxel for castration-sensitive prostate cancer and HRR gene alteration status. The study’s primary endpoint was imaging-based PFS (ibPFS) by blinded independent central review (BICR).

Overall, median ibPFS by BICR was significantly improved in the combination group in comparison with the patients who received placebo; it was not reached versus 21.9 months (hazard ratio, 0.63; P < .001). It was also significantly improved among the HRR-deficient subgroup (HR, 0.46; P < .001) as well as in the HRR-nondeficient or unknown (HR, 0.70; P = .004) and HRR-nondeficient patients by tumor tissue testing (HR, 0.66; P = .009).

Talazoparib plus enzalutamide was also favored with regard to other endpoints. Dr. Agarwal noted that, while overall survival data are as yet immature, objective response rates, PSA response of at least 50%, and time to PSA progression and use of subsequent cytotoxic chemotherapy and antineoplastic therapy significantly favored the talazoparib group.

The objective response rate was 61.7% versus 43.9% (P = .005), with 37.5% versus 18.2% complete responses.

“The higher rates of complete response suggest a cooperative effect of talazoparib plus enzalutamide treatment,” he explained.
 

High rate of adverse events

The rate of treatment-emergent adverse events was higher among patients who received talazoparib plus enzalutamide; 71.9% of the patients who received talazoparib plus enzalutamide experienced grade 3-4 TEAEs versus 40.6%. The most common grade 3 or greater TEAEs in the talazoparib group were anemia, low neutrophil counts, and low platelet counts. Hypertension, anemia, and fatigue were the most common in the placebo group. Talazoparib was discontinued in 19.1% of patients because of TEAEs. Enzalutamide was discontinued in 10.8% of patients in the combination group versus 11.0% in the placebo group.

Dr. Agarwal pointed out that there were TEAEs of special interest for talazoparib. “Myelodysplastic syndrome was reported in one patient during the safety reporting period, and acute myeloid leukemia was reported in one patient during the follow-up period,” he said.

Additionally, pulmonary embolism was reported in 10 (2.5%) patients (grade 3 in 9 patients) in the talazoparib arm and in 3 (0.7%) patients (all grade 3) in the placebo arm.
 

Results less relevant

Commenting on the study, Matthew Zibelman, MD, associate professor, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that these results represent an “intriguing finding for men with mCRPC, particularly in conjunction with the previously reported PROPEL study results.

“However, given that many patients receive an androgen receptor inhibitor now for metastatic castration-sensitive prostate cancer, these results are less relevant to current practice,” Dr. Zibelman said.

“Demonstration of an overall survival benefit of the combination would be optimal to change standard of care vs potential sequential therapy.”

The study was sponsored by Pfizer, manufacturer of enzalutamide and talazoparib. Dr. Agarwal has relationships with numerous pharmaceutical companies. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis and Pfizer, and Roche. Dr. Zibelman has relationships with Bristol-Myers Squibb, Exelixis, Pfizer, Jannsen, EMD Serono, and Blue Earth.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – New findings lend further support to adjuvant nivolumab (Opdivo) as a standard of care for patients with metastatic urothelial cancer.

Extended follow-up data from the phase 3 CheckMate 274 trial continue to show that, compared with placebo, nivolumab improves disease-free survival, nonurothelial tract recurrence-free survival (NUTRFS), and distant metastasis-free survival (DMFS) in patients with high-risk, muscle-invasive urothelial cancer after undergoing radical surgery.

The benefit was observed in both in the intent-to-treat population (ITT) and in the subset of patients with programmed death–ligand 1 (PD-L1) expression of at least 1%.

“In the ITT population, median disease-free survival with nivolumab was doubled compared to placebo,” said lead author Matthew Galsky, MD, director of genitourinary medical oncology and codirector of the Center of Excellence for Bladder Cancer at Tisch Cancer Institute, New York. “For the patients with high PD-L1 expression, the median disease-free survival with nivolumab reached 52.6 months, more than six times that of the placebo arm.

“These results further support adjuvant nivolumab as a standard of care in high-risk muscle-invasive urothelial cancer after resection,” he concluded.

Dr. Galsky presented the findings at the 2023 ASCO Genitourinary Cancers Symposium.

Practice changing

The earlier results of this study have already led to an approval from the Food and Drug Administration. In August 2021, nivolumab became the first adjuvant immunotherapy for use in patients with urothelial carcinoma at high risk for recurrence after radical resection

“This is a practice-changing study,” said Scot Niglio, MD, medical oncologist, New York University Perlmutter Cancer Center, who was approached for an independent comment.

“For decades, there were limited to zero treatment options in the postsurgical setting for urothelial cancer patients with a high recurrence risk,” he said.

The standard of care for muscle-invasive urothelial carcinoma is surgery, which may include neoadjuvant cisplatin-based chemotherapy, but most patients will experience disease recurrence, he explained.

“When urothelial cancer recurs outside the urinary tract, the prognosis quickly changes from curable to incurable,” he said, “making this area of research paramount.”

Dr. Niglio emphasized that these updated results show continued benefit from nivolumab on disease-free survival, as well as nonurothelial tract recurrence-free survival and distant metastasis-free survival, supporting its use as standard of care therapy.

“Even though the overall survival data is still maturing, the current data remains promising,” he said. “Patients with urothelial cancer meeting the criteria for high risk now have a treatment option to mitigate the potential of distant recurrence.”

In his own practice, Dr. Niglio added that he will “continue to discuss adjuvant nivolumab as a potential treatment option with all patients who are eligible based on this study.”
 

Met all endpoints

The Checkmate 274 trial involved 353 patients (of whom 140 patients had PD-L1 ≥ 1%) randomly assigned to take nivolumab 240 mg every 2 weeks and 356 patients (with 142 patients with PD-L1 ≥ 1%) randomized to placebo. All patients had pathologic evidence of urothelial cancer at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) of1 or less.

Previous results, at a median follow-up of about 20 months, show that the study met its primary endpoint, showing significant prolongation of disease-free survival in the intention-to-treat population, with nivolumab at 21 months versus placebo at 10.9 months (hazard ratio, 0.70; P < .001).

When the analysis considered only patients with tumors expressing PD-L1 of at least 1%, the median disease-free survival was even higher (not reached vs. 10.8 months; HR, 0.53; P < .001).

Nivolumab was also superior to placebo for NUTRFS, in both in the entire ITT population and in the subset with PD-L1–positive tumors.

The latest results come from a median follow-up of 36.1 months. The median disease-free survival was 22 months with nivolumab, compared with 10.9 months with placebo in ITT patients and 52.6 months on nivolumab versus 8.4 months in patients with PD-L1 of at least 1%.

Nivolumab was superior to placebo for secondary and exploratory endpoints, NUTRFS (ITT: HR, 0.72 and PD-L1 ≥ 1%: HR, 0.53) and DMFS (ITT: HR, 0.74; PD-L1 ≥ 1%: HR, 0.58). However, overall survival data remained immature and will be assessed as a future data cutoff, Dr. Galsky explained.

The updated analysis also included another exploratory endpoint, progression-free survival 2 (PFS2), defined as time from randomization to disease progression after subsequent next-line systemic therapy, start of second subsequent next-line systemic therapy, or death.

Median PFS2 was 61.2 months for all-patients who received nivolumab versus 47.1 months with placebo (HR, 0.79). In the PD-L1 of 1% or greater subgroup, median PFS2 was not reached with nivolumab versus 39.4 months with placebo (HR, 0.54).

Grade 3-4 treatment-related adverse events occurred in 18.2% and 7.2% of patients (nivolumab vs. placebo), and this was consistent with the primary analysis. “No new safety signals were identified,” said Dr. Galsky.

The CheckMate 274 trial was funded by Bristol-Myers Squibb, manufacturer of nivolumab. Dr. Galsky reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – New findings lend further support to adjuvant nivolumab (Opdivo) as a standard of care for patients with metastatic urothelial cancer.

Extended follow-up data from the phase 3 CheckMate 274 trial continue to show that, compared with placebo, nivolumab improves disease-free survival, nonurothelial tract recurrence-free survival (NUTRFS), and distant metastasis-free survival (DMFS) in patients with high-risk, muscle-invasive urothelial cancer after undergoing radical surgery.

The benefit was observed in both in the intent-to-treat population (ITT) and in the subset of patients with programmed death–ligand 1 (PD-L1) expression of at least 1%.

“In the ITT population, median disease-free survival with nivolumab was doubled compared to placebo,” said lead author Matthew Galsky, MD, director of genitourinary medical oncology and codirector of the Center of Excellence for Bladder Cancer at Tisch Cancer Institute, New York. “For the patients with high PD-L1 expression, the median disease-free survival with nivolumab reached 52.6 months, more than six times that of the placebo arm.

“These results further support adjuvant nivolumab as a standard of care in high-risk muscle-invasive urothelial cancer after resection,” he concluded.

Dr. Galsky presented the findings at the 2023 ASCO Genitourinary Cancers Symposium.

Practice changing

The earlier results of this study have already led to an approval from the Food and Drug Administration. In August 2021, nivolumab became the first adjuvant immunotherapy for use in patients with urothelial carcinoma at high risk for recurrence after radical resection

“This is a practice-changing study,” said Scot Niglio, MD, medical oncologist, New York University Perlmutter Cancer Center, who was approached for an independent comment.

“For decades, there were limited to zero treatment options in the postsurgical setting for urothelial cancer patients with a high recurrence risk,” he said.

The standard of care for muscle-invasive urothelial carcinoma is surgery, which may include neoadjuvant cisplatin-based chemotherapy, but most patients will experience disease recurrence, he explained.

“When urothelial cancer recurs outside the urinary tract, the prognosis quickly changes from curable to incurable,” he said, “making this area of research paramount.”

Dr. Niglio emphasized that these updated results show continued benefit from nivolumab on disease-free survival, as well as nonurothelial tract recurrence-free survival and distant metastasis-free survival, supporting its use as standard of care therapy.

“Even though the overall survival data is still maturing, the current data remains promising,” he said. “Patients with urothelial cancer meeting the criteria for high risk now have a treatment option to mitigate the potential of distant recurrence.”

In his own practice, Dr. Niglio added that he will “continue to discuss adjuvant nivolumab as a potential treatment option with all patients who are eligible based on this study.”
 

Met all endpoints

The Checkmate 274 trial involved 353 patients (of whom 140 patients had PD-L1 ≥ 1%) randomly assigned to take nivolumab 240 mg every 2 weeks and 356 patients (with 142 patients with PD-L1 ≥ 1%) randomized to placebo. All patients had pathologic evidence of urothelial cancer at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) of1 or less.

Previous results, at a median follow-up of about 20 months, show that the study met its primary endpoint, showing significant prolongation of disease-free survival in the intention-to-treat population, with nivolumab at 21 months versus placebo at 10.9 months (hazard ratio, 0.70; P < .001).

When the analysis considered only patients with tumors expressing PD-L1 of at least 1%, the median disease-free survival was even higher (not reached vs. 10.8 months; HR, 0.53; P < .001).

Nivolumab was also superior to placebo for NUTRFS, in both in the entire ITT population and in the subset with PD-L1–positive tumors.

The latest results come from a median follow-up of 36.1 months. The median disease-free survival was 22 months with nivolumab, compared with 10.9 months with placebo in ITT patients and 52.6 months on nivolumab versus 8.4 months in patients with PD-L1 of at least 1%.

Nivolumab was superior to placebo for secondary and exploratory endpoints, NUTRFS (ITT: HR, 0.72 and PD-L1 ≥ 1%: HR, 0.53) and DMFS (ITT: HR, 0.74; PD-L1 ≥ 1%: HR, 0.58). However, overall survival data remained immature and will be assessed as a future data cutoff, Dr. Galsky explained.

The updated analysis also included another exploratory endpoint, progression-free survival 2 (PFS2), defined as time from randomization to disease progression after subsequent next-line systemic therapy, start of second subsequent next-line systemic therapy, or death.

Median PFS2 was 61.2 months for all-patients who received nivolumab versus 47.1 months with placebo (HR, 0.79). In the PD-L1 of 1% or greater subgroup, median PFS2 was not reached with nivolumab versus 39.4 months with placebo (HR, 0.54).

Grade 3-4 treatment-related adverse events occurred in 18.2% and 7.2% of patients (nivolumab vs. placebo), and this was consistent with the primary analysis. “No new safety signals were identified,” said Dr. Galsky.

The CheckMate 274 trial was funded by Bristol-Myers Squibb, manufacturer of nivolumab. Dr. Galsky reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – New findings lend further support to adjuvant nivolumab (Opdivo) as a standard of care for patients with metastatic urothelial cancer.

Extended follow-up data from the phase 3 CheckMate 274 trial continue to show that, compared with placebo, nivolumab improves disease-free survival, nonurothelial tract recurrence-free survival (NUTRFS), and distant metastasis-free survival (DMFS) in patients with high-risk, muscle-invasive urothelial cancer after undergoing radical surgery.

The benefit was observed in both in the intent-to-treat population (ITT) and in the subset of patients with programmed death–ligand 1 (PD-L1) expression of at least 1%.

“In the ITT population, median disease-free survival with nivolumab was doubled compared to placebo,” said lead author Matthew Galsky, MD, director of genitourinary medical oncology and codirector of the Center of Excellence for Bladder Cancer at Tisch Cancer Institute, New York. “For the patients with high PD-L1 expression, the median disease-free survival with nivolumab reached 52.6 months, more than six times that of the placebo arm.

“These results further support adjuvant nivolumab as a standard of care in high-risk muscle-invasive urothelial cancer after resection,” he concluded.

Dr. Galsky presented the findings at the 2023 ASCO Genitourinary Cancers Symposium.

Practice changing

The earlier results of this study have already led to an approval from the Food and Drug Administration. In August 2021, nivolumab became the first adjuvant immunotherapy for use in patients with urothelial carcinoma at high risk for recurrence after radical resection

“This is a practice-changing study,” said Scot Niglio, MD, medical oncologist, New York University Perlmutter Cancer Center, who was approached for an independent comment.

“For decades, there were limited to zero treatment options in the postsurgical setting for urothelial cancer patients with a high recurrence risk,” he said.

The standard of care for muscle-invasive urothelial carcinoma is surgery, which may include neoadjuvant cisplatin-based chemotherapy, but most patients will experience disease recurrence, he explained.

“When urothelial cancer recurs outside the urinary tract, the prognosis quickly changes from curable to incurable,” he said, “making this area of research paramount.”

Dr. Niglio emphasized that these updated results show continued benefit from nivolumab on disease-free survival, as well as nonurothelial tract recurrence-free survival and distant metastasis-free survival, supporting its use as standard of care therapy.

“Even though the overall survival data is still maturing, the current data remains promising,” he said. “Patients with urothelial cancer meeting the criteria for high risk now have a treatment option to mitigate the potential of distant recurrence.”

In his own practice, Dr. Niglio added that he will “continue to discuss adjuvant nivolumab as a potential treatment option with all patients who are eligible based on this study.”
 

Met all endpoints

The Checkmate 274 trial involved 353 patients (of whom 140 patients had PD-L1 ≥ 1%) randomly assigned to take nivolumab 240 mg every 2 weeks and 356 patients (with 142 patients with PD-L1 ≥ 1%) randomized to placebo. All patients had pathologic evidence of urothelial cancer at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) of1 or less.

Previous results, at a median follow-up of about 20 months, show that the study met its primary endpoint, showing significant prolongation of disease-free survival in the intention-to-treat population, with nivolumab at 21 months versus placebo at 10.9 months (hazard ratio, 0.70; P < .001).

When the analysis considered only patients with tumors expressing PD-L1 of at least 1%, the median disease-free survival was even higher (not reached vs. 10.8 months; HR, 0.53; P < .001).

Nivolumab was also superior to placebo for NUTRFS, in both in the entire ITT population and in the subset with PD-L1–positive tumors.

The latest results come from a median follow-up of 36.1 months. The median disease-free survival was 22 months with nivolumab, compared with 10.9 months with placebo in ITT patients and 52.6 months on nivolumab versus 8.4 months in patients with PD-L1 of at least 1%.

Nivolumab was superior to placebo for secondary and exploratory endpoints, NUTRFS (ITT: HR, 0.72 and PD-L1 ≥ 1%: HR, 0.53) and DMFS (ITT: HR, 0.74; PD-L1 ≥ 1%: HR, 0.58). However, overall survival data remained immature and will be assessed as a future data cutoff, Dr. Galsky explained.

The updated analysis also included another exploratory endpoint, progression-free survival 2 (PFS2), defined as time from randomization to disease progression after subsequent next-line systemic therapy, start of second subsequent next-line systemic therapy, or death.

Median PFS2 was 61.2 months for all-patients who received nivolumab versus 47.1 months with placebo (HR, 0.79). In the PD-L1 of 1% or greater subgroup, median PFS2 was not reached with nivolumab versus 39.4 months with placebo (HR, 0.54).

Grade 3-4 treatment-related adverse events occurred in 18.2% and 7.2% of patients (nivolumab vs. placebo), and this was consistent with the primary analysis. “No new safety signals were identified,” said Dr. Galsky.

The CheckMate 274 trial was funded by Bristol-Myers Squibb, manufacturer of nivolumab. Dr. Galsky reported relationships with numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – For patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA alteration whose disease had already progressed with an androgen receptor pathway inhibitor (ARPI), imaging-based progression-free survival (PFS) was significantly longer through treatment with rucaparib (Rubraca, Clovis) than with any other drug chosen by their physician.

The finding, which comes from the TRITON3 clinical trial, provides evidence of clinical benefit for an indication for rucaparib that was granted an accelerated approval in May 2020.

“Rucaparib reduced the risk of progression or death by half in patients with BRCA alterations,” said lead author Alan H. Bryce, MD, medical director of the Genomic Oncology Clinic at Mayo Clinic Arizona, in Phoenix.

For the subgroup of patients with BRCA alterations, the median PFS was 11.2 months with rucaparib vs. 6.4 months (hazard ratio, 0.50; P < .001) among those who received physician’s choice of therapy, which included docetaxel or a second-generation ARPI, such as abiraterone or enzalutamide.

In another subgroup of patients whose disease had ATM alterations, the median PFS was 8.1 months with rucaparib vs. 6.8 months with physician’s choice of drug. The difference was not statistically significant.

However, the difference was significant in the intention-to-treat (ITT) population (comprising both subgroups), for whom the median PFS was 10.2 months with rucaparib vs. 6.4 months with physician’s choice of drug (HR, 0.61; P < .001 by log-rank test).

Dr. Bryce pointed out that three-quarters of the patients in the physician’s-choice arm who had progressive disease crossed over to rucaparib upon progression and that overall survival (OS) results are immature. At 62 months, median OS did not significantly differ in the BRCA subgroup (24.3 vs. 20.8 months favoring rucaparib; P = .21) or in the ITT group (23.6 vs. 20.9 months; P = .67).

Importantly, rucaparib was well tolerated. In all treatment groups, the most frequent adverse events were asthenia and fatigue, Bryce said. “There were no cases of myelodysplastic syndrome or acute myeloid leukemia reported.”

These results from the TRITON3 trial were presented at the 2023 ASCO Genitourinary Cancers Symposium and were published simultaneously in the New England Journal of Medicine.
 

Suggested benefit

Rucaparib is the first PARP inhibitor approved for use in patients with mCRPC that harbors deleterious BRCA mutations (germline and/or somatic) who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy. This prostate cancer indication was granted an accelerated approval in May 2020 by the U.S. Food and Drug Administration on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial, the forerunner of the current study.

The TRITON2 study was a single-arm clinical trial that involved three cohorts: 62 patients with a BRCA mutation (germline and/or somatic) and measurable disease; 115 patients with a BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency–positive mCRPC.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%. For the patients with measurable disease and a BRCA mutation, the objective response rate was 44%. The objective response rate was similar for those with a germline BRCA mutation.
 

Study details

The current phase 3 randomized TRITON3 clinical trial was conducted to confirm the earlier findings and to expand upon the data in mCRPC. The participants in this trial were patients with mCRPC who had specific gene alterations, including BRCA and ATM alterations, who had experienced disease progression after androgen receptor–directed therapy but who had not yet received chemotherapy.

A total of 270 men were assigned to receive rucaparib (600 mg twice daily); 135 patients received their physician’s choice of medication. Within the two study arms, 302 patients had a BRCA alteration, and 103 patients had an ATM alteration. The ITT population consisted of all the patients who had been randomly assigned to either of the two groups. A prespecified subgroup included patients with a BRCA alteration.

The primary outcome was the median duration of imaging-based PSF, as determined through independent review. Key secondary outcomes were overall survival and objective response rate.

The most common adverse events in the rucaparib group were fatigue, nausea, and anemia or decreased hemoglobin. In the control group, the most common adverse events were fatigue, diarrhea, and neuropathy. The most common events of grade 3 or higher were anemia or decreased hemoglobin, neutropenia or a decreased neutrophil count, and fatigue in the rucaparib group, and fatigue and neutropenia or a decreased neutrophil count among control patients.
 

No changes in standard of care

In a discussion of the study, Elena Castro, MD, PhD, of the Instituto de Investigación Biomédica de Málaga, Campanillas, Spain, emphasized that there is a clear benefit from the use of PARP inhibitors (such as rucaparib) for patients with BRCA alterations.

However, she highlighted the absence of convincing overall survival data and the absence of a clear benefit on PFS in the subgroup of patients with ATM alterations.

“These data raise several questions,” she noted, “such as, do patients with ATM alterations benefit at all? And should PARP inhibitors [such as rucaparib] precede or follow docetaxel therapy?”

Because of the high crossover rate, it may be possible to evaluate the directionality of docetaxel followed by PARP inhibitors and the other way around, she suggested.

Dr. Castro said that patients with BRCA alterations benefit from PARP inhibitors and are likely to derive more benefit from them than from taxanes.

“But those with ATM alterations are unlikely to benefit from rucaparib more than from taxanes,” she said.

In a comment, Hank Ng, MD, medical oncologist, NYU Langone Perlmutter Cancer Center, New York, said he is not convinced that the findings from TRITON 3 represent a new standard of care in BRCA 1/2 mutations or ATM.

“Currently, we know that, for patients with prostate cancer with BRCA1/2 or ATM, the standard of care is an androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide, then docetaxel, and then a PARP inhibitor like rucaparib,” he said.

(Currently, rucaparib is indicated for use in patients with mCRPC with BRCA alterations after they have already received an ARPI and taxane-based chemotherapy.)

Dr. Ng also questioned the control arm of the TRITON 3 trial. All the participants in the trial had already experienced disease progression after treatment with a second-generation ARPI. But the physician’s choice of therapy allowed them to move on to another ARPI or to docetaxel.

Dr. NG commented that, “in almost all cases, after progression of one ARPI, switching to another ARPI does not provide much benefit – from what is visible from this abstract – and only 56% patients received docetaxel, and thus 44% received a not-beneficial treatment,” he said.

“I am not sure what the docetaxel subgroup showed, but potentially, if those numbers are convincing, we could move this [rucaparib] ahead of docetaxel,” he speculated.

However, he also pointed out that an overall survival benefit has not yet been shown; so far, the benefit that has been shown is with respect to imaging-based PFS.

Dr. Ng does agree that rucaparib is indicated in the second line after progression with one ARPI for patients who are not candidates for chemotherapy. “But this has not yet shown me that we should absolutely be offering rucaparib before docetaxel,” he said.

TRITON3 was supported by Clovis Oncology, manufacturer of rucaparib. Dr. Bryce has relationships with Bayer, Foundation Medicine, Janssen, Merck, Myovant Sciences, and Novartis and holds a patent for therapeutic targeting of cancer patients with NRG1 rearrangements. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis, Pfizer, and Roche.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – For patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA alteration whose disease had already progressed with an androgen receptor pathway inhibitor (ARPI), imaging-based progression-free survival (PFS) was significantly longer through treatment with rucaparib (Rubraca, Clovis) than with any other drug chosen by their physician.

The finding, which comes from the TRITON3 clinical trial, provides evidence of clinical benefit for an indication for rucaparib that was granted an accelerated approval in May 2020.

“Rucaparib reduced the risk of progression or death by half in patients with BRCA alterations,” said lead author Alan H. Bryce, MD, medical director of the Genomic Oncology Clinic at Mayo Clinic Arizona, in Phoenix.

For the subgroup of patients with BRCA alterations, the median PFS was 11.2 months with rucaparib vs. 6.4 months (hazard ratio, 0.50; P < .001) among those who received physician’s choice of therapy, which included docetaxel or a second-generation ARPI, such as abiraterone or enzalutamide.

In another subgroup of patients whose disease had ATM alterations, the median PFS was 8.1 months with rucaparib vs. 6.8 months with physician’s choice of drug. The difference was not statistically significant.

However, the difference was significant in the intention-to-treat (ITT) population (comprising both subgroups), for whom the median PFS was 10.2 months with rucaparib vs. 6.4 months with physician’s choice of drug (HR, 0.61; P < .001 by log-rank test).

Dr. Bryce pointed out that three-quarters of the patients in the physician’s-choice arm who had progressive disease crossed over to rucaparib upon progression and that overall survival (OS) results are immature. At 62 months, median OS did not significantly differ in the BRCA subgroup (24.3 vs. 20.8 months favoring rucaparib; P = .21) or in the ITT group (23.6 vs. 20.9 months; P = .67).

Importantly, rucaparib was well tolerated. In all treatment groups, the most frequent adverse events were asthenia and fatigue, Bryce said. “There were no cases of myelodysplastic syndrome or acute myeloid leukemia reported.”

These results from the TRITON3 trial were presented at the 2023 ASCO Genitourinary Cancers Symposium and were published simultaneously in the New England Journal of Medicine.
 

Suggested benefit

Rucaparib is the first PARP inhibitor approved for use in patients with mCRPC that harbors deleterious BRCA mutations (germline and/or somatic) who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy. This prostate cancer indication was granted an accelerated approval in May 2020 by the U.S. Food and Drug Administration on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial, the forerunner of the current study.

The TRITON2 study was a single-arm clinical trial that involved three cohorts: 62 patients with a BRCA mutation (germline and/or somatic) and measurable disease; 115 patients with a BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency–positive mCRPC.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%. For the patients with measurable disease and a BRCA mutation, the objective response rate was 44%. The objective response rate was similar for those with a germline BRCA mutation.
 

Study details

The current phase 3 randomized TRITON3 clinical trial was conducted to confirm the earlier findings and to expand upon the data in mCRPC. The participants in this trial were patients with mCRPC who had specific gene alterations, including BRCA and ATM alterations, who had experienced disease progression after androgen receptor–directed therapy but who had not yet received chemotherapy.

A total of 270 men were assigned to receive rucaparib (600 mg twice daily); 135 patients received their physician’s choice of medication. Within the two study arms, 302 patients had a BRCA alteration, and 103 patients had an ATM alteration. The ITT population consisted of all the patients who had been randomly assigned to either of the two groups. A prespecified subgroup included patients with a BRCA alteration.

The primary outcome was the median duration of imaging-based PSF, as determined through independent review. Key secondary outcomes were overall survival and objective response rate.

The most common adverse events in the rucaparib group were fatigue, nausea, and anemia or decreased hemoglobin. In the control group, the most common adverse events were fatigue, diarrhea, and neuropathy. The most common events of grade 3 or higher were anemia or decreased hemoglobin, neutropenia or a decreased neutrophil count, and fatigue in the rucaparib group, and fatigue and neutropenia or a decreased neutrophil count among control patients.
 

No changes in standard of care

In a discussion of the study, Elena Castro, MD, PhD, of the Instituto de Investigación Biomédica de Málaga, Campanillas, Spain, emphasized that there is a clear benefit from the use of PARP inhibitors (such as rucaparib) for patients with BRCA alterations.

However, she highlighted the absence of convincing overall survival data and the absence of a clear benefit on PFS in the subgroup of patients with ATM alterations.

“These data raise several questions,” she noted, “such as, do patients with ATM alterations benefit at all? And should PARP inhibitors [such as rucaparib] precede or follow docetaxel therapy?”

Because of the high crossover rate, it may be possible to evaluate the directionality of docetaxel followed by PARP inhibitors and the other way around, she suggested.

Dr. Castro said that patients with BRCA alterations benefit from PARP inhibitors and are likely to derive more benefit from them than from taxanes.

“But those with ATM alterations are unlikely to benefit from rucaparib more than from taxanes,” she said.

In a comment, Hank Ng, MD, medical oncologist, NYU Langone Perlmutter Cancer Center, New York, said he is not convinced that the findings from TRITON 3 represent a new standard of care in BRCA 1/2 mutations or ATM.

“Currently, we know that, for patients with prostate cancer with BRCA1/2 or ATM, the standard of care is an androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide, then docetaxel, and then a PARP inhibitor like rucaparib,” he said.

(Currently, rucaparib is indicated for use in patients with mCRPC with BRCA alterations after they have already received an ARPI and taxane-based chemotherapy.)

Dr. Ng also questioned the control arm of the TRITON 3 trial. All the participants in the trial had already experienced disease progression after treatment with a second-generation ARPI. But the physician’s choice of therapy allowed them to move on to another ARPI or to docetaxel.

Dr. NG commented that, “in almost all cases, after progression of one ARPI, switching to another ARPI does not provide much benefit – from what is visible from this abstract – and only 56% patients received docetaxel, and thus 44% received a not-beneficial treatment,” he said.

“I am not sure what the docetaxel subgroup showed, but potentially, if those numbers are convincing, we could move this [rucaparib] ahead of docetaxel,” he speculated.

However, he also pointed out that an overall survival benefit has not yet been shown; so far, the benefit that has been shown is with respect to imaging-based PFS.

Dr. Ng does agree that rucaparib is indicated in the second line after progression with one ARPI for patients who are not candidates for chemotherapy. “But this has not yet shown me that we should absolutely be offering rucaparib before docetaxel,” he said.

TRITON3 was supported by Clovis Oncology, manufacturer of rucaparib. Dr. Bryce has relationships with Bayer, Foundation Medicine, Janssen, Merck, Myovant Sciences, and Novartis and holds a patent for therapeutic targeting of cancer patients with NRG1 rearrangements. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis, Pfizer, and Roche.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – For patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA alteration whose disease had already progressed with an androgen receptor pathway inhibitor (ARPI), imaging-based progression-free survival (PFS) was significantly longer through treatment with rucaparib (Rubraca, Clovis) than with any other drug chosen by their physician.

The finding, which comes from the TRITON3 clinical trial, provides evidence of clinical benefit for an indication for rucaparib that was granted an accelerated approval in May 2020.

“Rucaparib reduced the risk of progression or death by half in patients with BRCA alterations,” said lead author Alan H. Bryce, MD, medical director of the Genomic Oncology Clinic at Mayo Clinic Arizona, in Phoenix.

For the subgroup of patients with BRCA alterations, the median PFS was 11.2 months with rucaparib vs. 6.4 months (hazard ratio, 0.50; P < .001) among those who received physician’s choice of therapy, which included docetaxel or a second-generation ARPI, such as abiraterone or enzalutamide.

In another subgroup of patients whose disease had ATM alterations, the median PFS was 8.1 months with rucaparib vs. 6.8 months with physician’s choice of drug. The difference was not statistically significant.

However, the difference was significant in the intention-to-treat (ITT) population (comprising both subgroups), for whom the median PFS was 10.2 months with rucaparib vs. 6.4 months with physician’s choice of drug (HR, 0.61; P < .001 by log-rank test).

Dr. Bryce pointed out that three-quarters of the patients in the physician’s-choice arm who had progressive disease crossed over to rucaparib upon progression and that overall survival (OS) results are immature. At 62 months, median OS did not significantly differ in the BRCA subgroup (24.3 vs. 20.8 months favoring rucaparib; P = .21) or in the ITT group (23.6 vs. 20.9 months; P = .67).

Importantly, rucaparib was well tolerated. In all treatment groups, the most frequent adverse events were asthenia and fatigue, Bryce said. “There were no cases of myelodysplastic syndrome or acute myeloid leukemia reported.”

These results from the TRITON3 trial were presented at the 2023 ASCO Genitourinary Cancers Symposium and were published simultaneously in the New England Journal of Medicine.
 

Suggested benefit

Rucaparib is the first PARP inhibitor approved for use in patients with mCRPC that harbors deleterious BRCA mutations (germline and/or somatic) who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy. This prostate cancer indication was granted an accelerated approval in May 2020 by the U.S. Food and Drug Administration on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial, the forerunner of the current study.

The TRITON2 study was a single-arm clinical trial that involved three cohorts: 62 patients with a BRCA mutation (germline and/or somatic) and measurable disease; 115 patients with a BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency–positive mCRPC.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%. For the patients with measurable disease and a BRCA mutation, the objective response rate was 44%. The objective response rate was similar for those with a germline BRCA mutation.
 

Study details

The current phase 3 randomized TRITON3 clinical trial was conducted to confirm the earlier findings and to expand upon the data in mCRPC. The participants in this trial were patients with mCRPC who had specific gene alterations, including BRCA and ATM alterations, who had experienced disease progression after androgen receptor–directed therapy but who had not yet received chemotherapy.

A total of 270 men were assigned to receive rucaparib (600 mg twice daily); 135 patients received their physician’s choice of medication. Within the two study arms, 302 patients had a BRCA alteration, and 103 patients had an ATM alteration. The ITT population consisted of all the patients who had been randomly assigned to either of the two groups. A prespecified subgroup included patients with a BRCA alteration.

The primary outcome was the median duration of imaging-based PSF, as determined through independent review. Key secondary outcomes were overall survival and objective response rate.

The most common adverse events in the rucaparib group were fatigue, nausea, and anemia or decreased hemoglobin. In the control group, the most common adverse events were fatigue, diarrhea, and neuropathy. The most common events of grade 3 or higher were anemia or decreased hemoglobin, neutropenia or a decreased neutrophil count, and fatigue in the rucaparib group, and fatigue and neutropenia or a decreased neutrophil count among control patients.
 

No changes in standard of care

In a discussion of the study, Elena Castro, MD, PhD, of the Instituto de Investigación Biomédica de Málaga, Campanillas, Spain, emphasized that there is a clear benefit from the use of PARP inhibitors (such as rucaparib) for patients with BRCA alterations.

However, she highlighted the absence of convincing overall survival data and the absence of a clear benefit on PFS in the subgroup of patients with ATM alterations.

“These data raise several questions,” she noted, “such as, do patients with ATM alterations benefit at all? And should PARP inhibitors [such as rucaparib] precede or follow docetaxel therapy?”

Because of the high crossover rate, it may be possible to evaluate the directionality of docetaxel followed by PARP inhibitors and the other way around, she suggested.

Dr. Castro said that patients with BRCA alterations benefit from PARP inhibitors and are likely to derive more benefit from them than from taxanes.

“But those with ATM alterations are unlikely to benefit from rucaparib more than from taxanes,” she said.

In a comment, Hank Ng, MD, medical oncologist, NYU Langone Perlmutter Cancer Center, New York, said he is not convinced that the findings from TRITON 3 represent a new standard of care in BRCA 1/2 mutations or ATM.

“Currently, we know that, for patients with prostate cancer with BRCA1/2 or ATM, the standard of care is an androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide, then docetaxel, and then a PARP inhibitor like rucaparib,” he said.

(Currently, rucaparib is indicated for use in patients with mCRPC with BRCA alterations after they have already received an ARPI and taxane-based chemotherapy.)

Dr. Ng also questioned the control arm of the TRITON 3 trial. All the participants in the trial had already experienced disease progression after treatment with a second-generation ARPI. But the physician’s choice of therapy allowed them to move on to another ARPI or to docetaxel.

Dr. NG commented that, “in almost all cases, after progression of one ARPI, switching to another ARPI does not provide much benefit – from what is visible from this abstract – and only 56% patients received docetaxel, and thus 44% received a not-beneficial treatment,” he said.

“I am not sure what the docetaxel subgroup showed, but potentially, if those numbers are convincing, we could move this [rucaparib] ahead of docetaxel,” he speculated.

However, he also pointed out that an overall survival benefit has not yet been shown; so far, the benefit that has been shown is with respect to imaging-based PFS.

Dr. Ng does agree that rucaparib is indicated in the second line after progression with one ARPI for patients who are not candidates for chemotherapy. “But this has not yet shown me that we should absolutely be offering rucaparib before docetaxel,” he said.

TRITON3 was supported by Clovis Oncology, manufacturer of rucaparib. Dr. Bryce has relationships with Bayer, Foundation Medicine, Janssen, Merck, Myovant Sciences, and Novartis and holds a patent for therapeutic targeting of cancer patients with NRG1 rearrangements. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis, Pfizer, and Roche.

A version of this article first appeared on Medscape.com.