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Rankings of most common cancers to shift over next 20 years
The next 20 years will see a big shift in cancer type rankings, researchers predict.
At the moment, the most common cancers in the United States are breast, lung, prostate, colorectal, and melanoma.
the study authors predicted. Breast cancer will remain the top cancer to be diagnosed, lung cancer will drop from second to third, and colorectal cancer will remain at fourth.
These predicted rankings of cancer types by their total number of annual cases were published online April 7, 2021, in JAMA Network Open.
The authors also rank cancer type by mortality. Currently, most cancer deaths are caused by lung cancer, followed by colorectal, pancreatic, and breast. By 2040, the most notable change in cancer deaths is that liver and intrahepatic bile duct cancer, currently at sixth, will jump up to third.
Two decades from now, the ranking in terms of cancer deaths will be lung, pancreatic, liver and intrahepatic bile duct, and colorectal.
“Our findings reflect the shifting dynamics of cancer screening and treatment,” lead author Lola Rahib, PhD, a pancreatic cancer scientist at Cancer Commons, the advocacy nonprofit, commented in a press statement.
The new analysis used population-growth projections (based on 2010 U.S. Census data) and current population-based cancer incidence and death rates (from Surveillance, Epidemiology, and End Results 2014-2016) to calculate the changes in incidences and deaths to the year 2040.
The projected, estimated numbers are not ironclad, the researchers acknowledged.
“Our projections assume that the observed rates and trends [from recent years] don’t change over time,” Dr. Rahib said in an interview, but she pointed out that change may indeed happen.
“Any long-term projections should be considered with a grain of salt,” said Kim Miller, MPH, a surveillance research scientist at the American Cancer Society, who was approached for comment.
Dr. Miller explained that “cancer trends can sometimes rapidly change within a few years.” Projections just 2-4 years ahead are “extremely difficult” and those 20 years ahead are even more so, she added in an interview.
“We’re encouraged to see the projected decreases in deaths from lung, colorectal, and breast cancer in the coming years,” said coauthor Lynn Matrisian, PhD, MBA, chief science officer at the Pancreatic Cancer Action Network. “It’s time to shift focus to some of the less commonly diagnosed cancers with the lowest survival rates, like pancreatic and liver cancer.”
Difference in opinion on prostate cancer
The huge fall in the incidence of prostate cancer that the authors predict will come about as a result of changes in prostate-specific antigen (PSA)–screening recommendations over the last 15 years, they suggested.
“The most recent change in 2018 recommends that men aged 55-69 can make their own decisions regarding screening, but previous changes recommended against PSA screening,” said Dr. Rahib.
“These changes in screening guidelines have influenced the number of diagnoses of prostate cancer in recent years and will continue to do so to 2040,” Dr. Rahib commented.
Dr. Miller casts doubt on this prediction.
Using data through 2017, “we have seen that the patterns in prostate cancer incidence are already shifting from the steep declines we saw in the early 2010s,” she said. “I would use caution when interpreting the overall trends for prostate, because this cancer in particular is dramatically affected by changes in recommendations for screening with the PSA test.”
Screening has also influenced colorectal cancer incidence, the authors pointed out, saying that the uptake of colorectal cancer screening is associated with a decrease in the number of colorectal cancers and deaths out to 2040, as a result of effectiveness of screening.
For breast cancer, the authors highlighted the fact that, although the number of breast cancers will continue to increase, the number of breast cancer deaths will decrease. That ongoing trend is most likely attributable to increased screening and advancements in treatment.
The study was supported by the National Institutes of Health, National Cancer Institute, the Cancer Prevention and Research Institute of Texas, Cancer Commons and the Pancreatic Cancer Action Network. The study authors and Dr. Miller disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The next 20 years will see a big shift in cancer type rankings, researchers predict.
At the moment, the most common cancers in the United States are breast, lung, prostate, colorectal, and melanoma.
the study authors predicted. Breast cancer will remain the top cancer to be diagnosed, lung cancer will drop from second to third, and colorectal cancer will remain at fourth.
These predicted rankings of cancer types by their total number of annual cases were published online April 7, 2021, in JAMA Network Open.
The authors also rank cancer type by mortality. Currently, most cancer deaths are caused by lung cancer, followed by colorectal, pancreatic, and breast. By 2040, the most notable change in cancer deaths is that liver and intrahepatic bile duct cancer, currently at sixth, will jump up to third.
Two decades from now, the ranking in terms of cancer deaths will be lung, pancreatic, liver and intrahepatic bile duct, and colorectal.
“Our findings reflect the shifting dynamics of cancer screening and treatment,” lead author Lola Rahib, PhD, a pancreatic cancer scientist at Cancer Commons, the advocacy nonprofit, commented in a press statement.
The new analysis used population-growth projections (based on 2010 U.S. Census data) and current population-based cancer incidence and death rates (from Surveillance, Epidemiology, and End Results 2014-2016) to calculate the changes in incidences and deaths to the year 2040.
The projected, estimated numbers are not ironclad, the researchers acknowledged.
“Our projections assume that the observed rates and trends [from recent years] don’t change over time,” Dr. Rahib said in an interview, but she pointed out that change may indeed happen.
“Any long-term projections should be considered with a grain of salt,” said Kim Miller, MPH, a surveillance research scientist at the American Cancer Society, who was approached for comment.
Dr. Miller explained that “cancer trends can sometimes rapidly change within a few years.” Projections just 2-4 years ahead are “extremely difficult” and those 20 years ahead are even more so, she added in an interview.
“We’re encouraged to see the projected decreases in deaths from lung, colorectal, and breast cancer in the coming years,” said coauthor Lynn Matrisian, PhD, MBA, chief science officer at the Pancreatic Cancer Action Network. “It’s time to shift focus to some of the less commonly diagnosed cancers with the lowest survival rates, like pancreatic and liver cancer.”
Difference in opinion on prostate cancer
The huge fall in the incidence of prostate cancer that the authors predict will come about as a result of changes in prostate-specific antigen (PSA)–screening recommendations over the last 15 years, they suggested.
“The most recent change in 2018 recommends that men aged 55-69 can make their own decisions regarding screening, but previous changes recommended against PSA screening,” said Dr. Rahib.
“These changes in screening guidelines have influenced the number of diagnoses of prostate cancer in recent years and will continue to do so to 2040,” Dr. Rahib commented.
Dr. Miller casts doubt on this prediction.
Using data through 2017, “we have seen that the patterns in prostate cancer incidence are already shifting from the steep declines we saw in the early 2010s,” she said. “I would use caution when interpreting the overall trends for prostate, because this cancer in particular is dramatically affected by changes in recommendations for screening with the PSA test.”
Screening has also influenced colorectal cancer incidence, the authors pointed out, saying that the uptake of colorectal cancer screening is associated with a decrease in the number of colorectal cancers and deaths out to 2040, as a result of effectiveness of screening.
For breast cancer, the authors highlighted the fact that, although the number of breast cancers will continue to increase, the number of breast cancer deaths will decrease. That ongoing trend is most likely attributable to increased screening and advancements in treatment.
The study was supported by the National Institutes of Health, National Cancer Institute, the Cancer Prevention and Research Institute of Texas, Cancer Commons and the Pancreatic Cancer Action Network. The study authors and Dr. Miller disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The next 20 years will see a big shift in cancer type rankings, researchers predict.
At the moment, the most common cancers in the United States are breast, lung, prostate, colorectal, and melanoma.
the study authors predicted. Breast cancer will remain the top cancer to be diagnosed, lung cancer will drop from second to third, and colorectal cancer will remain at fourth.
These predicted rankings of cancer types by their total number of annual cases were published online April 7, 2021, in JAMA Network Open.
The authors also rank cancer type by mortality. Currently, most cancer deaths are caused by lung cancer, followed by colorectal, pancreatic, and breast. By 2040, the most notable change in cancer deaths is that liver and intrahepatic bile duct cancer, currently at sixth, will jump up to third.
Two decades from now, the ranking in terms of cancer deaths will be lung, pancreatic, liver and intrahepatic bile duct, and colorectal.
“Our findings reflect the shifting dynamics of cancer screening and treatment,” lead author Lola Rahib, PhD, a pancreatic cancer scientist at Cancer Commons, the advocacy nonprofit, commented in a press statement.
The new analysis used population-growth projections (based on 2010 U.S. Census data) and current population-based cancer incidence and death rates (from Surveillance, Epidemiology, and End Results 2014-2016) to calculate the changes in incidences and deaths to the year 2040.
The projected, estimated numbers are not ironclad, the researchers acknowledged.
“Our projections assume that the observed rates and trends [from recent years] don’t change over time,” Dr. Rahib said in an interview, but she pointed out that change may indeed happen.
“Any long-term projections should be considered with a grain of salt,” said Kim Miller, MPH, a surveillance research scientist at the American Cancer Society, who was approached for comment.
Dr. Miller explained that “cancer trends can sometimes rapidly change within a few years.” Projections just 2-4 years ahead are “extremely difficult” and those 20 years ahead are even more so, she added in an interview.
“We’re encouraged to see the projected decreases in deaths from lung, colorectal, and breast cancer in the coming years,” said coauthor Lynn Matrisian, PhD, MBA, chief science officer at the Pancreatic Cancer Action Network. “It’s time to shift focus to some of the less commonly diagnosed cancers with the lowest survival rates, like pancreatic and liver cancer.”
Difference in opinion on prostate cancer
The huge fall in the incidence of prostate cancer that the authors predict will come about as a result of changes in prostate-specific antigen (PSA)–screening recommendations over the last 15 years, they suggested.
“The most recent change in 2018 recommends that men aged 55-69 can make their own decisions regarding screening, but previous changes recommended against PSA screening,” said Dr. Rahib.
“These changes in screening guidelines have influenced the number of diagnoses of prostate cancer in recent years and will continue to do so to 2040,” Dr. Rahib commented.
Dr. Miller casts doubt on this prediction.
Using data through 2017, “we have seen that the patterns in prostate cancer incidence are already shifting from the steep declines we saw in the early 2010s,” she said. “I would use caution when interpreting the overall trends for prostate, because this cancer in particular is dramatically affected by changes in recommendations for screening with the PSA test.”
Screening has also influenced colorectal cancer incidence, the authors pointed out, saying that the uptake of colorectal cancer screening is associated with a decrease in the number of colorectal cancers and deaths out to 2040, as a result of effectiveness of screening.
For breast cancer, the authors highlighted the fact that, although the number of breast cancers will continue to increase, the number of breast cancer deaths will decrease. That ongoing trend is most likely attributable to increased screening and advancements in treatment.
The study was supported by the National Institutes of Health, National Cancer Institute, the Cancer Prevention and Research Institute of Texas, Cancer Commons and the Pancreatic Cancer Action Network. The study authors and Dr. Miller disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Starting April 5, patients can read your notes: 5 things to consider
Change in writing style is not mandated
The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.
Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”
This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.
Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
Clinicians don’t have to change writing style.
The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.
“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.
Everyday experience should guide clinicians when writing notes, said one expert.
“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.
According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”
Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.
However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
Some clinical notes can be withheld.
The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.
There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.
The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
Some patients are more likely readers.
Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.
“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.
A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.
Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
You are part of the avant garde.
The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.
“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.
In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.
It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
The start day will come, and you may not notice.
“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.
“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.
Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.
However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”
Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.
The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Change in writing style is not mandated
Change in writing style is not mandated
The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.
Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”
This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.
Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
Clinicians don’t have to change writing style.
The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.
“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.
Everyday experience should guide clinicians when writing notes, said one expert.
“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.
According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”
Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.
However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
Some clinical notes can be withheld.
The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.
There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.
The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
Some patients are more likely readers.
Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.
“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.
A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.
Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
You are part of the avant garde.
The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.
“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.
In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.
It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
The start day will come, and you may not notice.
“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.
“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.
Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.
However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”
Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.
The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.
Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”
This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.
Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
Clinicians don’t have to change writing style.
The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.
“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.
Everyday experience should guide clinicians when writing notes, said one expert.
“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.
According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”
Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.
However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
Some clinical notes can be withheld.
The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.
There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.
The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
Some patients are more likely readers.
Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.
“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.
A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.
Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
You are part of the avant garde.
The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.
“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.
In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.
It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
The start day will come, and you may not notice.
“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.
“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.
Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.
However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”
Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.
The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Huge, struggling breast cancer screening trial gets lifeline
But mammography trends can’t be ignored.
A controversial, big-budget breast cancer screening trial that has been chronically unable to attract enough female participants since its debut in 2017 got a vote of confidence from a special working group of the National Cancer Institute (NCI) on March 17.
The Tomosynthesis Mammography Imaging Screening Trial (TMIST) should continue, but with modification, the expert group concluded in its report.
The randomized trial, with an estimated cost of $100 million, compares two kinds of mammography screenings for breast cancer in healthy women. One group of patients is screened with digital breast tomosynthesis, also known as 3-D mammography; the other is screened with the older, less expensive 2-D digital technology.
Tomosynthesis is already considered superior in detecting small cancers and reducing callbacks and is increasingly being used in the real world, leading some experts in the field to say that TMIST is critically hampered by women’s and radiologists’ preference for 3-D mammography.
At a meeting of an NCI advisory board in September 2020, there was a suggestion that the federal agency may kill the trial.
But at the latest meeting, the working group proposed that the trial should live on.
One of the main problems with the trial has been recruitment; the recommended changes discussed at the meeting include reducing the number of women needed in the study (from 165,000 to 102,000), which would allow patient “accrual to be completed more quickly,” the working group noted. In addition, the target date for completing patient accrual would be moved to 2023, 3 years after the original completion date of 2020.
The group’s recommendations now go to NCI staff for scientific review. The NCI will then decide about implementing the proposed changes.
The trial, which is the NCI’s largest and most expensive screening study, has never come close to targeted monthly enrollment. It was enrolling fewer than 1,500 patients per month over a 2-year period, instead of the projected 5,500 per month, Philip Castle, PhD, MPH, director of the NCI’s Division of Cancer Prevention, said last year. He called for a review of TMIST’s “feasibility and relevance” in view of the increasing use of tomosynthesis in the United States, as well as other factors.
The new technology has been “rapidly adopted” by facilities in North America, the working group noted. As of December 2020, approximately 74% of breast cancer screening clinics in the United States had at least one tomosynthesis or 3-D system; 42% of the mammography machines were 3-D.
This trend of increasing use of 3-D machines might be too much for TMIST to surmount, said Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, in Seattle, who chaired the working group.
“We are worried the challenges [to patient accrual] may persist due to the increasing adoption of three-dimensional breast tomosynthesis in the United States over time,” she said during the working group’s virtual presentation of the report to the NCI’s Clinical Trials and Translational Research Advisory Committee.
Committee member Smita Bhatia, MD, PhD, of the University of Alabama at Birmingham, wondered, “What are the ongoing barriers that [TMIST investigators] are going to face beside recruitment?”
Dr. Davidson answered by speaking, again, about market penetration of tomosynthesis machines and suggested that the recruitment problems and the availability of 3-D mammography are intertwined.
“Is this a technology that has or will arrive, at which point it may not be very easy to put the genie back in the bottle?” she asked.
That question has already been answered – widespread use of tomosynthesis is here to stay, argued Daniel Kopans, MD, of Harvard Medical School, Boston, who invented digital breast tomosynthesis but no longer benefits financially from his invention because the patent has expired.
“The horse is out of the barn,” Dr. Kopans said in an interview. By the time the study results are available, digital mammography will be a tool of the past, he said.
TMIST is a trial “that should never have been started in the first place, and it’s failing,” he said. “I was hoping they [the NCI] would say, ‘Let’s stop this because there’s not enough accrual.’ But it looks like they’re not.”
“TMIST is a waste of money,” said Dr. Kopans, repeating a criticism he has made in the past.
A drop in study power
The new recommendations for TMIST come about 1 year after Medscape Medical News reported that the study was lagging in enrollment of both patients and participating sites/physicians.
Last year, two TMIST study investigators said it had been difficult enlisting sites, in part because many radiologists and facilities – informed by their experience and previous research results – already believe that the 3-D technology is superior.
Currently, most 3-D systems are used in conjunction with 2-D. First, two static images of the breast are taken (2-D), and then the unit moves in an arc, taking multiple images of the breast (3-D). Thus, 3-D is widely described as allowing clinicians to flip through the images like “pages in a book” and as offering a superior read of the breast.
The NCI working group concedes that “there is evidence that screening utilizing tomosynthesis may reduce recall rates and improve cancer detection,” but it says the trial is needed to address “questions that still remain regarding the overall benefit to patients.”
Furthermore, tomosynthesis “may carry higher out-of-pocket costs for women and is more labor intensive and costly for health care systems in that it requires about twice as much reader time for interpretation,” the working group said.
The “main hypothesis of TMIST” is that “tomosynthesis will decrease the cumulative incidence of advanced breast cancers, a surrogate for mortality, compared to standard digital mammography,” posits the group.
Advanced breast cancer is defined in TMIST as invasive breast cancers that meet any of the following criteria:
- Distant metastases
- At least one lymph node macrometastasis
- Tumor size >1 cm and triple-negative or positive for human epidermal growth factor receptor
- Tumor size ≥ 20 mm unless of pure mucinous or other favorable histologies.
In the original study design, the sample size was estimated to be sufficient to provide 90% power to detect a 20% relative reduction in the proportion of advanced cancers in the intervention arm (tomosynthesis, or 3-D) compared to the control arm (digital mammography, or 2-D) 4.5 years from randomization.
Now, with fewer patients and a revised analytic approach, the study’s statistical power will be decreased to 80% from the original 90%.
Also, an advanced cancer is counted “if it occurs at any time while the participant is on study.”
Dr. Kopans says that is a problem.
“That is a huge mistake, since digital breast tomosynthesis cannot impact prevalent cancers. They are already there. This means that their ‘power calculation’ is wrong, and they won’t have the power that they are claiming,” he said.
Dr. Kopans explained that the first screen in TMIST will have “no effect on the number of advanced cancers.” That’s because the cancers will have already grown enough to become advanced, he said.
On the other hand, an initial screening might detect and thus lead to the removal of nonadvanced, smaller cancers, which, had they not been detected and removed, would have grown to become advanced cancers by the next year. Thus, the screenings done after the first year are the ones that potentially prove the effect of the intervention.
However, the working group report says that changes to the study will not affect anything other than a 10% reduction in the study’s power.
The working group is concerned about TMIST going on for years and years. For that reason, they recommended that the NCI establish “strict criteria for termination of the study” if accrual goals are not met. However, those parameters have not been developed, and it was not part of the study group’s mission to establish them.
The working group was sponsored by the NCI. Dr. Kopans reports consulting with DART Imaging in China.
A version of this article first appeared on Medscape.com.
But mammography trends can’t be ignored.
But mammography trends can’t be ignored.
A controversial, big-budget breast cancer screening trial that has been chronically unable to attract enough female participants since its debut in 2017 got a vote of confidence from a special working group of the National Cancer Institute (NCI) on March 17.
The Tomosynthesis Mammography Imaging Screening Trial (TMIST) should continue, but with modification, the expert group concluded in its report.
The randomized trial, with an estimated cost of $100 million, compares two kinds of mammography screenings for breast cancer in healthy women. One group of patients is screened with digital breast tomosynthesis, also known as 3-D mammography; the other is screened with the older, less expensive 2-D digital technology.
Tomosynthesis is already considered superior in detecting small cancers and reducing callbacks and is increasingly being used in the real world, leading some experts in the field to say that TMIST is critically hampered by women’s and radiologists’ preference for 3-D mammography.
At a meeting of an NCI advisory board in September 2020, there was a suggestion that the federal agency may kill the trial.
But at the latest meeting, the working group proposed that the trial should live on.
One of the main problems with the trial has been recruitment; the recommended changes discussed at the meeting include reducing the number of women needed in the study (from 165,000 to 102,000), which would allow patient “accrual to be completed more quickly,” the working group noted. In addition, the target date for completing patient accrual would be moved to 2023, 3 years after the original completion date of 2020.
The group’s recommendations now go to NCI staff for scientific review. The NCI will then decide about implementing the proposed changes.
The trial, which is the NCI’s largest and most expensive screening study, has never come close to targeted monthly enrollment. It was enrolling fewer than 1,500 patients per month over a 2-year period, instead of the projected 5,500 per month, Philip Castle, PhD, MPH, director of the NCI’s Division of Cancer Prevention, said last year. He called for a review of TMIST’s “feasibility and relevance” in view of the increasing use of tomosynthesis in the United States, as well as other factors.
The new technology has been “rapidly adopted” by facilities in North America, the working group noted. As of December 2020, approximately 74% of breast cancer screening clinics in the United States had at least one tomosynthesis or 3-D system; 42% of the mammography machines were 3-D.
This trend of increasing use of 3-D machines might be too much for TMIST to surmount, said Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, in Seattle, who chaired the working group.
“We are worried the challenges [to patient accrual] may persist due to the increasing adoption of three-dimensional breast tomosynthesis in the United States over time,” she said during the working group’s virtual presentation of the report to the NCI’s Clinical Trials and Translational Research Advisory Committee.
Committee member Smita Bhatia, MD, PhD, of the University of Alabama at Birmingham, wondered, “What are the ongoing barriers that [TMIST investigators] are going to face beside recruitment?”
Dr. Davidson answered by speaking, again, about market penetration of tomosynthesis machines and suggested that the recruitment problems and the availability of 3-D mammography are intertwined.
“Is this a technology that has or will arrive, at which point it may not be very easy to put the genie back in the bottle?” she asked.
That question has already been answered – widespread use of tomosynthesis is here to stay, argued Daniel Kopans, MD, of Harvard Medical School, Boston, who invented digital breast tomosynthesis but no longer benefits financially from his invention because the patent has expired.
“The horse is out of the barn,” Dr. Kopans said in an interview. By the time the study results are available, digital mammography will be a tool of the past, he said.
TMIST is a trial “that should never have been started in the first place, and it’s failing,” he said. “I was hoping they [the NCI] would say, ‘Let’s stop this because there’s not enough accrual.’ But it looks like they’re not.”
“TMIST is a waste of money,” said Dr. Kopans, repeating a criticism he has made in the past.
A drop in study power
The new recommendations for TMIST come about 1 year after Medscape Medical News reported that the study was lagging in enrollment of both patients and participating sites/physicians.
Last year, two TMIST study investigators said it had been difficult enlisting sites, in part because many radiologists and facilities – informed by their experience and previous research results – already believe that the 3-D technology is superior.
Currently, most 3-D systems are used in conjunction with 2-D. First, two static images of the breast are taken (2-D), and then the unit moves in an arc, taking multiple images of the breast (3-D). Thus, 3-D is widely described as allowing clinicians to flip through the images like “pages in a book” and as offering a superior read of the breast.
The NCI working group concedes that “there is evidence that screening utilizing tomosynthesis may reduce recall rates and improve cancer detection,” but it says the trial is needed to address “questions that still remain regarding the overall benefit to patients.”
Furthermore, tomosynthesis “may carry higher out-of-pocket costs for women and is more labor intensive and costly for health care systems in that it requires about twice as much reader time for interpretation,” the working group said.
The “main hypothesis of TMIST” is that “tomosynthesis will decrease the cumulative incidence of advanced breast cancers, a surrogate for mortality, compared to standard digital mammography,” posits the group.
Advanced breast cancer is defined in TMIST as invasive breast cancers that meet any of the following criteria:
- Distant metastases
- At least one lymph node macrometastasis
- Tumor size >1 cm and triple-negative or positive for human epidermal growth factor receptor
- Tumor size ≥ 20 mm unless of pure mucinous or other favorable histologies.
In the original study design, the sample size was estimated to be sufficient to provide 90% power to detect a 20% relative reduction in the proportion of advanced cancers in the intervention arm (tomosynthesis, or 3-D) compared to the control arm (digital mammography, or 2-D) 4.5 years from randomization.
Now, with fewer patients and a revised analytic approach, the study’s statistical power will be decreased to 80% from the original 90%.
Also, an advanced cancer is counted “if it occurs at any time while the participant is on study.”
Dr. Kopans says that is a problem.
“That is a huge mistake, since digital breast tomosynthesis cannot impact prevalent cancers. They are already there. This means that their ‘power calculation’ is wrong, and they won’t have the power that they are claiming,” he said.
Dr. Kopans explained that the first screen in TMIST will have “no effect on the number of advanced cancers.” That’s because the cancers will have already grown enough to become advanced, he said.
On the other hand, an initial screening might detect and thus lead to the removal of nonadvanced, smaller cancers, which, had they not been detected and removed, would have grown to become advanced cancers by the next year. Thus, the screenings done after the first year are the ones that potentially prove the effect of the intervention.
However, the working group report says that changes to the study will not affect anything other than a 10% reduction in the study’s power.
The working group is concerned about TMIST going on for years and years. For that reason, they recommended that the NCI establish “strict criteria for termination of the study” if accrual goals are not met. However, those parameters have not been developed, and it was not part of the study group’s mission to establish them.
The working group was sponsored by the NCI. Dr. Kopans reports consulting with DART Imaging in China.
A version of this article first appeared on Medscape.com.
A controversial, big-budget breast cancer screening trial that has been chronically unable to attract enough female participants since its debut in 2017 got a vote of confidence from a special working group of the National Cancer Institute (NCI) on March 17.
The Tomosynthesis Mammography Imaging Screening Trial (TMIST) should continue, but with modification, the expert group concluded in its report.
The randomized trial, with an estimated cost of $100 million, compares two kinds of mammography screenings for breast cancer in healthy women. One group of patients is screened with digital breast tomosynthesis, also known as 3-D mammography; the other is screened with the older, less expensive 2-D digital technology.
Tomosynthesis is already considered superior in detecting small cancers and reducing callbacks and is increasingly being used in the real world, leading some experts in the field to say that TMIST is critically hampered by women’s and radiologists’ preference for 3-D mammography.
At a meeting of an NCI advisory board in September 2020, there was a suggestion that the federal agency may kill the trial.
But at the latest meeting, the working group proposed that the trial should live on.
One of the main problems with the trial has been recruitment; the recommended changes discussed at the meeting include reducing the number of women needed in the study (from 165,000 to 102,000), which would allow patient “accrual to be completed more quickly,” the working group noted. In addition, the target date for completing patient accrual would be moved to 2023, 3 years after the original completion date of 2020.
The group’s recommendations now go to NCI staff for scientific review. The NCI will then decide about implementing the proposed changes.
The trial, which is the NCI’s largest and most expensive screening study, has never come close to targeted monthly enrollment. It was enrolling fewer than 1,500 patients per month over a 2-year period, instead of the projected 5,500 per month, Philip Castle, PhD, MPH, director of the NCI’s Division of Cancer Prevention, said last year. He called for a review of TMIST’s “feasibility and relevance” in view of the increasing use of tomosynthesis in the United States, as well as other factors.
The new technology has been “rapidly adopted” by facilities in North America, the working group noted. As of December 2020, approximately 74% of breast cancer screening clinics in the United States had at least one tomosynthesis or 3-D system; 42% of the mammography machines were 3-D.
This trend of increasing use of 3-D machines might be too much for TMIST to surmount, said Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, in Seattle, who chaired the working group.
“We are worried the challenges [to patient accrual] may persist due to the increasing adoption of three-dimensional breast tomosynthesis in the United States over time,” she said during the working group’s virtual presentation of the report to the NCI’s Clinical Trials and Translational Research Advisory Committee.
Committee member Smita Bhatia, MD, PhD, of the University of Alabama at Birmingham, wondered, “What are the ongoing barriers that [TMIST investigators] are going to face beside recruitment?”
Dr. Davidson answered by speaking, again, about market penetration of tomosynthesis machines and suggested that the recruitment problems and the availability of 3-D mammography are intertwined.
“Is this a technology that has or will arrive, at which point it may not be very easy to put the genie back in the bottle?” she asked.
That question has already been answered – widespread use of tomosynthesis is here to stay, argued Daniel Kopans, MD, of Harvard Medical School, Boston, who invented digital breast tomosynthesis but no longer benefits financially from his invention because the patent has expired.
“The horse is out of the barn,” Dr. Kopans said in an interview. By the time the study results are available, digital mammography will be a tool of the past, he said.
TMIST is a trial “that should never have been started in the first place, and it’s failing,” he said. “I was hoping they [the NCI] would say, ‘Let’s stop this because there’s not enough accrual.’ But it looks like they’re not.”
“TMIST is a waste of money,” said Dr. Kopans, repeating a criticism he has made in the past.
A drop in study power
The new recommendations for TMIST come about 1 year after Medscape Medical News reported that the study was lagging in enrollment of both patients and participating sites/physicians.
Last year, two TMIST study investigators said it had been difficult enlisting sites, in part because many radiologists and facilities – informed by their experience and previous research results – already believe that the 3-D technology is superior.
Currently, most 3-D systems are used in conjunction with 2-D. First, two static images of the breast are taken (2-D), and then the unit moves in an arc, taking multiple images of the breast (3-D). Thus, 3-D is widely described as allowing clinicians to flip through the images like “pages in a book” and as offering a superior read of the breast.
The NCI working group concedes that “there is evidence that screening utilizing tomosynthesis may reduce recall rates and improve cancer detection,” but it says the trial is needed to address “questions that still remain regarding the overall benefit to patients.”
Furthermore, tomosynthesis “may carry higher out-of-pocket costs for women and is more labor intensive and costly for health care systems in that it requires about twice as much reader time for interpretation,” the working group said.
The “main hypothesis of TMIST” is that “tomosynthesis will decrease the cumulative incidence of advanced breast cancers, a surrogate for mortality, compared to standard digital mammography,” posits the group.
Advanced breast cancer is defined in TMIST as invasive breast cancers that meet any of the following criteria:
- Distant metastases
- At least one lymph node macrometastasis
- Tumor size >1 cm and triple-negative or positive for human epidermal growth factor receptor
- Tumor size ≥ 20 mm unless of pure mucinous or other favorable histologies.
In the original study design, the sample size was estimated to be sufficient to provide 90% power to detect a 20% relative reduction in the proportion of advanced cancers in the intervention arm (tomosynthesis, or 3-D) compared to the control arm (digital mammography, or 2-D) 4.5 years from randomization.
Now, with fewer patients and a revised analytic approach, the study’s statistical power will be decreased to 80% from the original 90%.
Also, an advanced cancer is counted “if it occurs at any time while the participant is on study.”
Dr. Kopans says that is a problem.
“That is a huge mistake, since digital breast tomosynthesis cannot impact prevalent cancers. They are already there. This means that their ‘power calculation’ is wrong, and they won’t have the power that they are claiming,” he said.
Dr. Kopans explained that the first screen in TMIST will have “no effect on the number of advanced cancers.” That’s because the cancers will have already grown enough to become advanced, he said.
On the other hand, an initial screening might detect and thus lead to the removal of nonadvanced, smaller cancers, which, had they not been detected and removed, would have grown to become advanced cancers by the next year. Thus, the screenings done after the first year are the ones that potentially prove the effect of the intervention.
However, the working group report says that changes to the study will not affect anything other than a 10% reduction in the study’s power.
The working group is concerned about TMIST going on for years and years. For that reason, they recommended that the NCI establish “strict criteria for termination of the study” if accrual goals are not met. However, those parameters have not been developed, and it was not part of the study group’s mission to establish them.
The working group was sponsored by the NCI. Dr. Kopans reports consulting with DART Imaging in China.
A version of this article first appeared on Medscape.com.
Pembrolizumab SCLC indication withdrawn in U.S.
The move does not affect any of the drug’s other indications. The immunotherapy is used in the treatment of many different types of cancer.
The SCLC indication had been granted an accelerated approval by the Food and Drug Administration in 2019 based on tumor response rate and durability of response data from patient cohorts in two trials. However, the anti-PD-1 therapy failed to demonstrate statistically significant improved overall survival in a confirmatory trial, which is mandated after an accelerated approval.
The FDA is conducting “an industry-wide evaluation of indications based on accelerated approvals that have not yet met their postmarketing requirements,” said Merck.
In February of 2021, an indication for durvalumab (Imfinzi) was withdrawn by AstraZeneca in concert with the FDA after the drug failed to improve overall survival in unresectable metastatic bladder cancer in a confirmatory trial, as reported by Medscape Medical News.
“We will continue to rigorously evaluate the benefits of [pembrolizumab] in small cell lung cancer and other types of cancer, in pursuit of Merck’s mission to save and improve lives,” Roy Baynes, MD, chief medical officer, Merck Research Laboratories, said in the company statement
Dr. Baynes also championed the value of accelerated approvals.
“The accelerated pathways created by the FDA have been integral to the remarkable progress in oncology care over the past 5 years and have helped many cancer patients with advanced disease, including small cell lung cancer, access new treatments,” he said.
However, in the past, the FDA has been criticized for approving new cancer drugs based on surrogate markers such as response rates because, in many cases, subsequent studies often show that the drug fails to improve overall survival.
For example, a 2015 study found that 36 (67%) of 54 cancer drug approvals from 2008 to 2012 were made on the basis of surrogate markers – either tumor response rate or progression-free survival. Over a median follow-up period of 4.4 years, only 5 of those 36 drugs were shown in randomized studies to improve overall survival, as reported by Medscape Medical News.
The FDA says that it instituted the accelerated approval program to “allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint.” The program was started in 1992, in the midst of the HIV/AIDS epidemic.
In 2020, the nonprofit Friends of Cancer Research issued a white paper calling for reform in the accelerated approval process, which included a proposal to add risk assessment to surrogate endpoints that would factor in variables such as toxicity.
A version of this article first appeared on Medscape.com.
The move does not affect any of the drug’s other indications. The immunotherapy is used in the treatment of many different types of cancer.
The SCLC indication had been granted an accelerated approval by the Food and Drug Administration in 2019 based on tumor response rate and durability of response data from patient cohorts in two trials. However, the anti-PD-1 therapy failed to demonstrate statistically significant improved overall survival in a confirmatory trial, which is mandated after an accelerated approval.
The FDA is conducting “an industry-wide evaluation of indications based on accelerated approvals that have not yet met their postmarketing requirements,” said Merck.
In February of 2021, an indication for durvalumab (Imfinzi) was withdrawn by AstraZeneca in concert with the FDA after the drug failed to improve overall survival in unresectable metastatic bladder cancer in a confirmatory trial, as reported by Medscape Medical News.
“We will continue to rigorously evaluate the benefits of [pembrolizumab] in small cell lung cancer and other types of cancer, in pursuit of Merck’s mission to save and improve lives,” Roy Baynes, MD, chief medical officer, Merck Research Laboratories, said in the company statement
Dr. Baynes also championed the value of accelerated approvals.
“The accelerated pathways created by the FDA have been integral to the remarkable progress in oncology care over the past 5 years and have helped many cancer patients with advanced disease, including small cell lung cancer, access new treatments,” he said.
However, in the past, the FDA has been criticized for approving new cancer drugs based on surrogate markers such as response rates because, in many cases, subsequent studies often show that the drug fails to improve overall survival.
For example, a 2015 study found that 36 (67%) of 54 cancer drug approvals from 2008 to 2012 were made on the basis of surrogate markers – either tumor response rate or progression-free survival. Over a median follow-up period of 4.4 years, only 5 of those 36 drugs were shown in randomized studies to improve overall survival, as reported by Medscape Medical News.
The FDA says that it instituted the accelerated approval program to “allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint.” The program was started in 1992, in the midst of the HIV/AIDS epidemic.
In 2020, the nonprofit Friends of Cancer Research issued a white paper calling for reform in the accelerated approval process, which included a proposal to add risk assessment to surrogate endpoints that would factor in variables such as toxicity.
A version of this article first appeared on Medscape.com.
The move does not affect any of the drug’s other indications. The immunotherapy is used in the treatment of many different types of cancer.
The SCLC indication had been granted an accelerated approval by the Food and Drug Administration in 2019 based on tumor response rate and durability of response data from patient cohorts in two trials. However, the anti-PD-1 therapy failed to demonstrate statistically significant improved overall survival in a confirmatory trial, which is mandated after an accelerated approval.
The FDA is conducting “an industry-wide evaluation of indications based on accelerated approvals that have not yet met their postmarketing requirements,” said Merck.
In February of 2021, an indication for durvalumab (Imfinzi) was withdrawn by AstraZeneca in concert with the FDA after the drug failed to improve overall survival in unresectable metastatic bladder cancer in a confirmatory trial, as reported by Medscape Medical News.
“We will continue to rigorously evaluate the benefits of [pembrolizumab] in small cell lung cancer and other types of cancer, in pursuit of Merck’s mission to save and improve lives,” Roy Baynes, MD, chief medical officer, Merck Research Laboratories, said in the company statement
Dr. Baynes also championed the value of accelerated approvals.
“The accelerated pathways created by the FDA have been integral to the remarkable progress in oncology care over the past 5 years and have helped many cancer patients with advanced disease, including small cell lung cancer, access new treatments,” he said.
However, in the past, the FDA has been criticized for approving new cancer drugs based on surrogate markers such as response rates because, in many cases, subsequent studies often show that the drug fails to improve overall survival.
For example, a 2015 study found that 36 (67%) of 54 cancer drug approvals from 2008 to 2012 were made on the basis of surrogate markers – either tumor response rate or progression-free survival. Over a median follow-up period of 4.4 years, only 5 of those 36 drugs were shown in randomized studies to improve overall survival, as reported by Medscape Medical News.
The FDA says that it instituted the accelerated approval program to “allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint.” The program was started in 1992, in the midst of the HIV/AIDS epidemic.
In 2020, the nonprofit Friends of Cancer Research issued a white paper calling for reform in the accelerated approval process, which included a proposal to add risk assessment to surrogate endpoints that would factor in variables such as toxicity.
A version of this article first appeared on Medscape.com.
Bladder cancer indication withdrawn for durvalumab
The change does not affect this indication outside the United States, nor does it affect other approved durvalumab indications within the United States.
For example, durvalumab remains approved by the Food and Drug Administration in the curative-intent setting of unresectable, stage III non–small cell lung cancer after chemoradiotherapy and for the treatment of extensive-stage small cell lung cancer.
AstraZeneca is continuing with clinical trials of durvalumab in various combinations for the treatment of bladder cancer.
Granted accelerated approval
Durvalumab was granted accelerated approval in May 2017 by the FDA specifically for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with that chemotherapy.
That accelerated approval was based on the surrogate markers of tumor response rate and duration of response from Study 1108, a phase 1/2 trial. In this trial, the overall response rate was 17.8% in a cohort of 191 patients with locally advanced or metastatic urothelial cancer that had progressed during or after a platinum-based regimen.
However, in the confirmatory phase 3 DANUBE trial in patients with unresectable metastatic bladder cancer, neither durvalumab nor durvalumab plus tremelimumab met the primary endpoint of improving overall survival in comparison with standard-of-care chemotherapy.
“While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said in a company press statement.
A version of this article first appeared on Medscape.com.
The change does not affect this indication outside the United States, nor does it affect other approved durvalumab indications within the United States.
For example, durvalumab remains approved by the Food and Drug Administration in the curative-intent setting of unresectable, stage III non–small cell lung cancer after chemoradiotherapy and for the treatment of extensive-stage small cell lung cancer.
AstraZeneca is continuing with clinical trials of durvalumab in various combinations for the treatment of bladder cancer.
Granted accelerated approval
Durvalumab was granted accelerated approval in May 2017 by the FDA specifically for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with that chemotherapy.
That accelerated approval was based on the surrogate markers of tumor response rate and duration of response from Study 1108, a phase 1/2 trial. In this trial, the overall response rate was 17.8% in a cohort of 191 patients with locally advanced or metastatic urothelial cancer that had progressed during or after a platinum-based regimen.
However, in the confirmatory phase 3 DANUBE trial in patients with unresectable metastatic bladder cancer, neither durvalumab nor durvalumab plus tremelimumab met the primary endpoint of improving overall survival in comparison with standard-of-care chemotherapy.
“While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said in a company press statement.
A version of this article first appeared on Medscape.com.
The change does not affect this indication outside the United States, nor does it affect other approved durvalumab indications within the United States.
For example, durvalumab remains approved by the Food and Drug Administration in the curative-intent setting of unresectable, stage III non–small cell lung cancer after chemoradiotherapy and for the treatment of extensive-stage small cell lung cancer.
AstraZeneca is continuing with clinical trials of durvalumab in various combinations for the treatment of bladder cancer.
Granted accelerated approval
Durvalumab was granted accelerated approval in May 2017 by the FDA specifically for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with that chemotherapy.
That accelerated approval was based on the surrogate markers of tumor response rate and duration of response from Study 1108, a phase 1/2 trial. In this trial, the overall response rate was 17.8% in a cohort of 191 patients with locally advanced or metastatic urothelial cancer that had progressed during or after a platinum-based regimen.
However, in the confirmatory phase 3 DANUBE trial in patients with unresectable metastatic bladder cancer, neither durvalumab nor durvalumab plus tremelimumab met the primary endpoint of improving overall survival in comparison with standard-of-care chemotherapy.
“While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said in a company press statement.
A version of this article first appeared on Medscape.com.
Obesity ‘clearly’ not tied to worse survival in metastatic breast cancer
First large cohort study
The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.
Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.
Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”
However, underweight was independently associated with worse OS (median, 33 months; hazard ratio, 1.14; 95% confidence interval, 1.02-1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.
In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.
“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to this news organization.
The study was published online Dec. 1 in The Breast.
“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, who was asked for comment.
Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?
No, said Dr. Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better. … They just didn’t have worse outcomes.”
The study authors point out that the opposite is true in early-stage breast cancer. In this patient population, excess weight is associated with worse outcomes.
For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk, 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.
Why is there such a contrast between early- and late-stage disease?
“I don’t think we know exactly,” answered Dr. Ligibel. “It may be that, with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.
“Obesity and overweight are associated with cancer risk in general,” said Dr. Ligibel, citing more than a dozen malignancies, including breast cancer.
But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Dr. Ligibel noted.
That age-based difference is a conundrum, said Dr. Ligibel: “People have been trying to figure that out for a long time.”
Dr. Ligibel summarized as follows:
“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that, by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”
More study details
The findings come from the French National Epidemiological Strategy and Medical Economics–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.
A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m2), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0).
A total of 20% of women were obese, which is a much lower percentage than the 40%-50% that would be expected in a comparable American cohort, said Dr. Ligibel. Also, 5% of the French cohort was underweight.
Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).
As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight or obesity had no effect.
“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Dr. Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”
The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that, in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.
The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that, among women with a similar BMI, some might be muscular, whereas others might have more body fat.
Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from AstraZeneca, Daiichi Sankyo, Eisai, MSD, Pfizer, and Roche. Dr. Ligibel reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
First large cohort study
First large cohort study
The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.
Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.
Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”
However, underweight was independently associated with worse OS (median, 33 months; hazard ratio, 1.14; 95% confidence interval, 1.02-1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.
In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.
“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to this news organization.
The study was published online Dec. 1 in The Breast.
“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, who was asked for comment.
Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?
No, said Dr. Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better. … They just didn’t have worse outcomes.”
The study authors point out that the opposite is true in early-stage breast cancer. In this patient population, excess weight is associated with worse outcomes.
For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk, 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.
Why is there such a contrast between early- and late-stage disease?
“I don’t think we know exactly,” answered Dr. Ligibel. “It may be that, with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.
“Obesity and overweight are associated with cancer risk in general,” said Dr. Ligibel, citing more than a dozen malignancies, including breast cancer.
But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Dr. Ligibel noted.
That age-based difference is a conundrum, said Dr. Ligibel: “People have been trying to figure that out for a long time.”
Dr. Ligibel summarized as follows:
“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that, by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”
More study details
The findings come from the French National Epidemiological Strategy and Medical Economics–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.
A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m2), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0).
A total of 20% of women were obese, which is a much lower percentage than the 40%-50% that would be expected in a comparable American cohort, said Dr. Ligibel. Also, 5% of the French cohort was underweight.
Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).
As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight or obesity had no effect.
“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Dr. Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”
The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that, in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.
The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that, among women with a similar BMI, some might be muscular, whereas others might have more body fat.
Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from AstraZeneca, Daiichi Sankyo, Eisai, MSD, Pfizer, and Roche. Dr. Ligibel reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.
Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.
Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”
However, underweight was independently associated with worse OS (median, 33 months; hazard ratio, 1.14; 95% confidence interval, 1.02-1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.
In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.
“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to this news organization.
The study was published online Dec. 1 in The Breast.
“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, who was asked for comment.
Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?
No, said Dr. Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better. … They just didn’t have worse outcomes.”
The study authors point out that the opposite is true in early-stage breast cancer. In this patient population, excess weight is associated with worse outcomes.
For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk, 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.
Why is there such a contrast between early- and late-stage disease?
“I don’t think we know exactly,” answered Dr. Ligibel. “It may be that, with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.
“Obesity and overweight are associated with cancer risk in general,” said Dr. Ligibel, citing more than a dozen malignancies, including breast cancer.
But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Dr. Ligibel noted.
That age-based difference is a conundrum, said Dr. Ligibel: “People have been trying to figure that out for a long time.”
Dr. Ligibel summarized as follows:
“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that, by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”
More study details
The findings come from the French National Epidemiological Strategy and Medical Economics–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.
A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m2), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0).
A total of 20% of women were obese, which is a much lower percentage than the 40%-50% that would be expected in a comparable American cohort, said Dr. Ligibel. Also, 5% of the French cohort was underweight.
Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).
As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight or obesity had no effect.
“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Dr. Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”
The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that, in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.
The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that, among women with a similar BMI, some might be muscular, whereas others might have more body fat.
Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from AstraZeneca, Daiichi Sankyo, Eisai, MSD, Pfizer, and Roche. Dr. Ligibel reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Case study: Maternal cervical cancer linked to neonate lung cancer
That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.
“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.
Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.
In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.
Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.
“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”
Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”
Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.
“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.
“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.
In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.
How do the investigators know that the spread happened vaginally and not via the placenta?
They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.
That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”
In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.
“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.
C-section question
The first of the cases reported by the Japanese team was a toddler (23 months) who presented to a local hospital with a 2-week history of a productive cough. Computed tomography revealed multiple masses scattered along the bronchi in both lungs, and a biopsy revealed neuroendocrine carcinoma of the lung.
Notably, the mother’s cervical cancer was not diagnosed during her pregnancy. A cervical cytologic test performed in the mother 7 months before the birth was negative. The infant was delivered transvaginally at 39 weeks of gestation.
It was only 3 months after the birth that the 35-year-old mother received a diagnosis of squamous cell carcinoma of the cervix. She then underwent radical hysterectomy with pelvic lymphadenectomy, followed by chemotherapy.
Had it been known that she had cervical cancer, she may have been advised to have a cesarean section.
The study authors propose, on the basis of their paper, that all women with cervical cancer should have a cesarean section.
But a U.S. expert questioned this, and said the situation is “a bit nuanced.”
William Grobman, MD, of Northwestern University in Chicago, said the current standard recommendation for many pregnant women known to have cervical cancer is to have a cesarean section and that “the strength of the recommendation is dependent on factors such as stage and size.”
However, in an interview, he added that “it may be premature to make a blanket recommendation for all people based on two reports without any idea of the frequency of this event, and with such uncertainty, it seems that disclosure of all information and shared decision-making would be a key approach.”
In this case report, the authors also noted that the cancer found in the toddler looked similar to the cancer in the mother.
“Histologic similarities between the tumor samples from the mother and child prompted us to compare the results of their next-generation sequencing tests,” they said.
The result? “The comparison of the gene profiles in the samples of tumor and normal tissue confirmed that transmission of maternal tumor to the child had occurred.”
The lung cancer in the toddler progressed despite two chemotherapy regimens, so he was enrolled in a clinical trial of nivolumab therapy. He had a response that continued for 7 months, with no appearance of new lesions. Lobectomy was performed to resect a single remaining nodule. The boy had no evidence of disease recurrence at 12 months after lobectomy.
His mother was also enrolled in a nivolumab trial, but her cervical cancer had spread, and she died 5 months after disease progression.
Second case
In the second reported case, a 6-year-old boy presented to a local hospital with chest pain on the left side. Computed tomography revealed a mass in the left lung, and mucinous adenocarcinoma was eventually diagnosed.
In this case, the mother had a cervical polypoid tumor detected during pregnancy. But, as in the other case, cervical cytologic analysis was negative. Because the tumor was stable without any intervention, the mother delivered the boy vaginally at 38 weeks of gestation.
However, after the delivery, biopsy of the cervical lesion revealed adenocarcinoma. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy 3 months after delivery. She died of the disease 2 years after the surgery.
The boy received chemotherapy and had a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels. But 3 months later, the disease recurred in the left lung. After more chemotherapy, he underwent total left pneumonectomy and was subsequently free of disease.
The study authors said that they did not suspect maternal transmission of the cancer when her child received a diagnosis at 6 years of age. They explained that metastatic cervical cancer is typically a fast-growing tumor and the slow growth in the child seemed inconsistent with the idea that the cancer had been transmitted to him.
However, the pathology exam showed that the boy had mucinous adenocarcinoma, “which is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother,” the authors reported.
Samples of the cervical tumor from the mother and from the lung tumor of the child were submitted for next-generation sequencing tests and, said the authors, indicated mother-to-infant transmission.
The study was supported by grants from the Japan Agency for Medical Research and Development; the National Cancer Center Research and Development Fund; and the Ministry of Education, Culture, Sports, Science and Technology; and funding from Ono Pharmaceutical.
A version of this article first appeared on Medscape.com.
That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.
“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.
Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.
In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.
Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.
“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”
Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”
Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.
“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.
“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.
In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.
How do the investigators know that the spread happened vaginally and not via the placenta?
They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.
That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”
In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.
“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.
C-section question
The first of the cases reported by the Japanese team was a toddler (23 months) who presented to a local hospital with a 2-week history of a productive cough. Computed tomography revealed multiple masses scattered along the bronchi in both lungs, and a biopsy revealed neuroendocrine carcinoma of the lung.
Notably, the mother’s cervical cancer was not diagnosed during her pregnancy. A cervical cytologic test performed in the mother 7 months before the birth was negative. The infant was delivered transvaginally at 39 weeks of gestation.
It was only 3 months after the birth that the 35-year-old mother received a diagnosis of squamous cell carcinoma of the cervix. She then underwent radical hysterectomy with pelvic lymphadenectomy, followed by chemotherapy.
Had it been known that she had cervical cancer, she may have been advised to have a cesarean section.
The study authors propose, on the basis of their paper, that all women with cervical cancer should have a cesarean section.
But a U.S. expert questioned this, and said the situation is “a bit nuanced.”
William Grobman, MD, of Northwestern University in Chicago, said the current standard recommendation for many pregnant women known to have cervical cancer is to have a cesarean section and that “the strength of the recommendation is dependent on factors such as stage and size.”
However, in an interview, he added that “it may be premature to make a blanket recommendation for all people based on two reports without any idea of the frequency of this event, and with such uncertainty, it seems that disclosure of all information and shared decision-making would be a key approach.”
In this case report, the authors also noted that the cancer found in the toddler looked similar to the cancer in the mother.
“Histologic similarities between the tumor samples from the mother and child prompted us to compare the results of their next-generation sequencing tests,” they said.
The result? “The comparison of the gene profiles in the samples of tumor and normal tissue confirmed that transmission of maternal tumor to the child had occurred.”
The lung cancer in the toddler progressed despite two chemotherapy regimens, so he was enrolled in a clinical trial of nivolumab therapy. He had a response that continued for 7 months, with no appearance of new lesions. Lobectomy was performed to resect a single remaining nodule. The boy had no evidence of disease recurrence at 12 months after lobectomy.
His mother was also enrolled in a nivolumab trial, but her cervical cancer had spread, and she died 5 months after disease progression.
Second case
In the second reported case, a 6-year-old boy presented to a local hospital with chest pain on the left side. Computed tomography revealed a mass in the left lung, and mucinous adenocarcinoma was eventually diagnosed.
In this case, the mother had a cervical polypoid tumor detected during pregnancy. But, as in the other case, cervical cytologic analysis was negative. Because the tumor was stable without any intervention, the mother delivered the boy vaginally at 38 weeks of gestation.
However, after the delivery, biopsy of the cervical lesion revealed adenocarcinoma. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy 3 months after delivery. She died of the disease 2 years after the surgery.
The boy received chemotherapy and had a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels. But 3 months later, the disease recurred in the left lung. After more chemotherapy, he underwent total left pneumonectomy and was subsequently free of disease.
The study authors said that they did not suspect maternal transmission of the cancer when her child received a diagnosis at 6 years of age. They explained that metastatic cervical cancer is typically a fast-growing tumor and the slow growth in the child seemed inconsistent with the idea that the cancer had been transmitted to him.
However, the pathology exam showed that the boy had mucinous adenocarcinoma, “which is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother,” the authors reported.
Samples of the cervical tumor from the mother and from the lung tumor of the child were submitted for next-generation sequencing tests and, said the authors, indicated mother-to-infant transmission.
The study was supported by grants from the Japan Agency for Medical Research and Development; the National Cancer Center Research and Development Fund; and the Ministry of Education, Culture, Sports, Science and Technology; and funding from Ono Pharmaceutical.
A version of this article first appeared on Medscape.com.
That’s the conclusion of two ground-breaking cases from Japan in which investigators describe lung cancer in two boys that “probably developed” from their respective mothers via vaginal transmission during birth.
“Transmission of maternal cancer to offspring is extremely rare and is estimated to occur in approximately 1 infant per every 500,000 mothers with cancer,” wrote Ayumu Arakawa, MD, of the National Cancer Center Hospital in Japan, and colleagues, in a paper published Jan. 7 in The New England Journal of Medicine.
Previous cases, of which only 18 have been recorded, have been presumed to occur via transplacental transmission, they said.
In the two new cases, genetic analyses and other evidence suggest that both boys’ lung cancers developed after aspirating uterine cervical cancer tumor cells into their lungs during passage through the birth canal.
Tragically, both mothers, each of whom was diagnosed with cervical cancer after the births, died while their boys were still infants.
“Most of the maternal-to-infant cases reported have been leukemia or melanoma,” said Mel Greaves, PhD, of the Institute of Cancer Research, London, who was asked for comment. In 2009, Dr. Greaves and colleagues published a case study of maternal-to-infant cancer transmission (presumably via the placenta). “It attracted an enormous amount of publicity and no doubt some alarm,” he said in an interview. He emphasized that the phenomenon is “incredibly rare.”
Dr. Greaves explains why such transmission is so rare. “We suspect that cancer cells do transit from mum to unborn child more often, but the foreign (aka paternal) antigens (HLA) on the tumor cells prompt immunological rejection. The extremely rare cases of successful transmission probably do depend on the fortuitous loss of paternal HLA.”
Advances in genetic technology may allow such cases, which have been recorded since 1950, to be rapidly identified now, he said.
“Where there is an adult-type cancer in an infant or child whose mother carried cancer when pregnant, then whole-genome sequencing should quickly tell if the infant’s tumor was of maternal origin,” Dr. Greaves explained.
“I think we will be seeing more reports like this in the future, now that this phenomenon has been described and next-generation sequencing is more readily available,” added Mae Zakhour, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, when asked for comment.
In the case of the Japanese boys, both cases were discovered incidentally during an analysis of the results of routine next-generation sequencing testing in a prospective gene-profiling trial in cancer patients, known as TOP-GEAR.
How do the investigators know that the spread happened vaginally and not via the placenta?
They explained that, in other cases of mother-to-fetus transmission, the offspring presented with multiple metastases in the brain, bones, liver, lungs, and soft tissues, which were “consistent with presumed hematogenous spread from the placenta.” However, in the two boys, tumors were observed only in the lungs and were localized along the bronchi.
That peribronchial pattern of tumor growth “suggested that the tumors arose from mother-to-infant vaginal transmission through aspiration of tumor-contaminated vaginal fluids during birth.”
In addition, the tumors in both boys lacked the Y chromosome and shared multiple somatic mutations, an HPV genome, and SNP alleles with tumors from the mothers.
“The identical molecular profiles of maternal and pediatric tumors demonstrated by next-generation sequencing, as well as the location of the tumors in the children, provides strong evidence for cancer transmission during delivery,” Dr. Zakhour summarized.
C-section question
The first of the cases reported by the Japanese team was a toddler (23 months) who presented to a local hospital with a 2-week history of a productive cough. Computed tomography revealed multiple masses scattered along the bronchi in both lungs, and a biopsy revealed neuroendocrine carcinoma of the lung.
Notably, the mother’s cervical cancer was not diagnosed during her pregnancy. A cervical cytologic test performed in the mother 7 months before the birth was negative. The infant was delivered transvaginally at 39 weeks of gestation.
It was only 3 months after the birth that the 35-year-old mother received a diagnosis of squamous cell carcinoma of the cervix. She then underwent radical hysterectomy with pelvic lymphadenectomy, followed by chemotherapy.
Had it been known that she had cervical cancer, she may have been advised to have a cesarean section.
The study authors propose, on the basis of their paper, that all women with cervical cancer should have a cesarean section.
But a U.S. expert questioned this, and said the situation is “a bit nuanced.”
William Grobman, MD, of Northwestern University in Chicago, said the current standard recommendation for many pregnant women known to have cervical cancer is to have a cesarean section and that “the strength of the recommendation is dependent on factors such as stage and size.”
However, in an interview, he added that “it may be premature to make a blanket recommendation for all people based on two reports without any idea of the frequency of this event, and with such uncertainty, it seems that disclosure of all information and shared decision-making would be a key approach.”
In this case report, the authors also noted that the cancer found in the toddler looked similar to the cancer in the mother.
“Histologic similarities between the tumor samples from the mother and child prompted us to compare the results of their next-generation sequencing tests,” they said.
The result? “The comparison of the gene profiles in the samples of tumor and normal tissue confirmed that transmission of maternal tumor to the child had occurred.”
The lung cancer in the toddler progressed despite two chemotherapy regimens, so he was enrolled in a clinical trial of nivolumab therapy. He had a response that continued for 7 months, with no appearance of new lesions. Lobectomy was performed to resect a single remaining nodule. The boy had no evidence of disease recurrence at 12 months after lobectomy.
His mother was also enrolled in a nivolumab trial, but her cervical cancer had spread, and she died 5 months after disease progression.
Second case
In the second reported case, a 6-year-old boy presented to a local hospital with chest pain on the left side. Computed tomography revealed a mass in the left lung, and mucinous adenocarcinoma was eventually diagnosed.
In this case, the mother had a cervical polypoid tumor detected during pregnancy. But, as in the other case, cervical cytologic analysis was negative. Because the tumor was stable without any intervention, the mother delivered the boy vaginally at 38 weeks of gestation.
However, after the delivery, biopsy of the cervical lesion revealed adenocarcinoma. The mother underwent radical hysterectomy and bilateral salpingo-oophorectomy 3 months after delivery. She died of the disease 2 years after the surgery.
The boy received chemotherapy and had a partial response, with a reduction in levels of the tumor marker CA19-9 to normal levels. But 3 months later, the disease recurred in the left lung. After more chemotherapy, he underwent total left pneumonectomy and was subsequently free of disease.
The study authors said that they did not suspect maternal transmission of the cancer when her child received a diagnosis at 6 years of age. They explained that metastatic cervical cancer is typically a fast-growing tumor and the slow growth in the child seemed inconsistent with the idea that the cancer had been transmitted to him.
However, the pathology exam showed that the boy had mucinous adenocarcinoma, “which is an unusual morphologic finding for a primary lung tumor, but it was similar to the uterine cervical tumor in the mother,” the authors reported.
Samples of the cervical tumor from the mother and from the lung tumor of the child were submitted for next-generation sequencing tests and, said the authors, indicated mother-to-infant transmission.
The study was supported by grants from the Japan Agency for Medical Research and Development; the National Cancer Center Research and Development Fund; and the Ministry of Education, Culture, Sports, Science and Technology; and funding from Ono Pharmaceutical.
A version of this article first appeared on Medscape.com.
After 48 years, NCI aims to track breast cancer recurrences
Change to SEER eventually planned.
Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.
“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.
But those statistics have not been available from a robust population-based source.
Now, there is hope that they will – at last – be collected.
A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.
But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.
“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.
“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.
But this database has never included information on cancer recurrence.
In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
New project
The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.
The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.
She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.
“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
Why the change now?
“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.
Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.
Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.
In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
Tracking recurrences
In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.
Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.
“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.
To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.
On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.
Nonetheless, these clinical trials provide a starting place.
The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.
The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.
“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.
The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.
The study was supported by NCI.
A version of this article first appeared on Medscape.com.
Change to SEER eventually planned.
Change to SEER eventually planned.
Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.
“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.
But those statistics have not been available from a robust population-based source.
Now, there is hope that they will – at last – be collected.
A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.
But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.
“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.
“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.
But this database has never included information on cancer recurrence.
In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
New project
The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.
The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.
She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.
“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
Why the change now?
“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.
Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.
Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.
In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
Tracking recurrences
In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.
Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.
“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.
To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.
On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.
Nonetheless, these clinical trials provide a starting place.
The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.
The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.
“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.
The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.
The study was supported by NCI.
A version of this article first appeared on Medscape.com.
Patients with breast cancer want accurate information on the risk of their cancer recurring once they have completed treatment.
“I would like to know the true stats of how many breast cancers come back no matter what the hell we do for treatment,” comments a typical post on a breast cancer patient bulletin board.
But those statistics have not been available from a robust population-based source.
Now, there is hope that they will – at last – be collected.
A new pilot project at the National Cancer Institute is setting out to collect that information, although the researchers say it is a “long-term goal” that will take a few years.
But it has already been a long time coming. The mother lode of all U.S. cancer data, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program, started collecting cancer data in 1973.
“When they began to capture cancer data, the focus was primarily on the incidence of cancer, the different types of cancer, and survival,” explained Esmeralda Ramirez-Pena, PhD, MPH, cancer prevention fellow at the NCI.
“Later, SEER expanded to include subgroups of various cancers and different stages at diagnosis,” she added.
But this database has never included information on cancer recurrence.
In a 2017 press statement, the NCI commented: “Collecting recurrence data has been challenging for cancer registries because recurrence can be diagnosed through diverse methods and in a variety of locations.”
New project
The NCI now has a “long-term goal” to implement additional “data elements” into SEER that will allow calculation of breast cancer recurrences, said Dr. Ramirez-Pena.
The Breast Cancer Recurrence Project, a pilot program funded via an NCI–Department of Energy collaboration, “will take a couple of years,” she said.
She presented some details of the new project as a poster at the recent San Antonio Breast Cancer Symposium 2020.
“SEER has added data elements over time,” she said, and this latest move will – at last – include information on breast cancer recurrence.
Why the change now?
“There’s been so much interest [in breast cancer recurrence]. It’s a top cause of cancer death in the United States and globally. The urgent need is evident,” she explained.
Breast cancer advocates have long been calling for SEER to count recurrence, including metastatic recurrence.
Katherine O’Brien, a breast cancer “metser” from Chicago, is credited with especially turning the heat up on the NCI.
In 2015, Ms. O’Brien spearheaded the creation of an online petition on the website change.org, calling on the NCI’s SEER, the Centers for Disease Control and Prevention, and all state cancer registries to start counting all people living with metastatic breast cancer, including those whose early-stage disease progressed. The petition, which is now closed, collected nearly 12,000 signatures.
Tracking recurrences
In the new project, cancer recurrence is defined as a cancer that was treated, reduced to undetectable levels, and later returned either locally, regionally, or distantly.
Tracking recurrence is not a simple matter because posttreatment surveillance to detect it includes clinical exams, biomarker testing, pathologic studies, molecular testing, imaging, and patient-reported symptoms and because recurrence frequency varies by subtype of breast cancer and TNM classification. Additionally, recurrence may depend on age at diagnosis, a variety of risk factors, treatment type, and access to quality of care.
“It’s likely there are many elements that influence recurrence,” said Dr. Ramirez-Pena.
To get a handle on the complexity, the NCI needs to first identify which data are needed to tally recurrence and the frequency at which they are collected, explained Dr. Ramirez-Pena. To do so, she and her coinvestigators conducted a systematic review of phase 3 clinical trials of early-stage breast cancer.
On their own, such trials are not sufficient to provide recurrence estimates at the population level because they lack diversity, represent fewer than 5% of all cancer patients, and the study period may not be long enough to capture recurrences for long-latency breast cancers, such as estrogen receptor–positive malignancies.
Nonetheless, these clinical trials provide a starting place.
The investigators identified 444 early-stage clinical trials. They stratified participants by subtype and tumor characteristics, which will enable analysis of risk-group and treatment-dependent differences in recurrence.
The changing science of breast cancer makes this work a challenge, the investigators said. For example, in clinical trials from the early 1990s through the early 2000s, receptor status and subtyping was not commonly reported, and some treatment endpoints were added during the past few years.
“Our next step will be to extract recurrence rates from these trials so we can eventually provide individualized information about recurrence risk to survivors,” Dr. Ramirez-Pena said, describing the big-picture aims.
The Breast Cancer Recurrence Project is collaborating with external agencies, such as the International Agency for Research on Cancer and Public Health England, in fine-tuning data elements, because “recurrence is not captured well globally either,” said Dr. Ramirez-Pena.
The study was supported by NCI.
A version of this article first appeared on Medscape.com.
‘Contrary’ to wide belief, abscopal effect is rare in cancer
The phase 2, single-center study was conducted in 62 patients with head and neck cancer and at least two metastatic lesions. They were randomly assigned to receive nivolumab with or without additional radiation, delivered as stereotactic body radiation therapy (SBRT), but directed at only one of the metastatic lesions.
The results showed a similar rate of tumor shrinkage and disappearance in both groups (34.5% for nivolumab vs. 29.0% for the combination; P = .86) reported Sean McBride, MD, MPH, Memorial Sloan Kettering Cancer Center, New York, and colleagues in a paper published online in the Journal of Clinical Oncology.
The finding indicates that there was no abscopal effect, the team concluded.
The abscopal (from the Latin ab “away from” and scopus “target”) effect, first described in the 1950s, is a hypothetical result of radiation, whereby tumors situated outside the radiation field are reduced or eliminated by an assumed reaction mediated by the immune system.
This study is only the second randomized controlled trial to look at this effect. A previous trial in lung cancer (JAMA Oncol. 2019;5:1276) also failed to show a significant difference in objective response rate, the primary outcome.
In both studies, there was also no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of radiation.
“There are still die-hard proponents of the existence of an abscopal response, but it is clear from our data – there is no abscopal response,” lead study author Nancy Lee, MD, said in an interview.
Dr. Lee, also from Memorial Sloan Kettering, was referring to this trial in head and neck cancer specifically. But previous nonrandomized studies have also reported response rates for the combination of SBRT and immunotherapy that are similar to monotherapy, the authors point out. Overall, the collective data in oncology suggest that the abscopal response is “relatively rare,” the team comments.
A more emphatic statement comes from a pair of oncologists in an accompanying editorial.
The new study “provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare,” wrote Tanguy Seiwert, MD, medical oncologist, and Ana Kiess, MD, PhD, radiation oncologist, both at Johns Hopkins University, Baltimore.
This is a “well-executed study that has broader implications beyond head and neck cancer and speaks to larger issues of combination therapies in the era of cancer immunotherapy,” they also wrote.
The practice of using limited SBRT on any tumor type – along with anti–PD-1/PD-L1 therapy – “should not be pursued for the sole purpose of induction of an abscopal effect until we have better data to support any benefit,” the editorialists added.
It’s time to put the abscopal effect to rest, suggested Dr. Lee.
“Instead of focusing on whether an abscopal response exists or not, as it clearly did not in our phase 2 study, our focus should shift to the broader picture. What is the optimal timing of PD-1 or PD-L1 therapy in relation to radiotherapy?” she said.
The answer appears to be sequentially – and not concurrently, which is how radiation has been used to induce the would-be abscopal effect, she explained. “I personally feel that immunotherapy should not be given concurrently with radiation therapy.”
Damning data for the concurrent approach come from the phase 3 Javelin Head and Neck 100 trial, she said. In March, trial sponsors announced that the trial was terminated as it was unlikely to meet its primary endpoint. Specifically, adding an anti–PD-L1 therapy to chemoradiotherapy was not superior to chemoradiotherapy alone.
On the other hand, in the phase 3 lung cancer study known as PACIFIC, chemoradiotherapy followed by sequential anti–PD-L1 therapy showed “dramatic” improvements in PFS and OS, the editorialists pointed out.
Radiation and immunotherapy combinations
Despite the failure of this trial, radiation has “significant potential for combination with immunotherapy,” observed Dr. Seiwert and Dr. Kiess.
There are at least three potential roles of radiation therapy in combination with anti–PD-1/PD-L1 therapy, they wrote.
They explained that the first is single-site palliative radiation therapy/SBRT, which can control local symptoms. The second is “consolidation” of all tumor sites with radiation therapy/SBRT, which may decrease tumor burden and heterogeneity. And the third potential role is definitive locoregional radiation therapy to achieve long-term locoregional tumor control.
Thus, the editorialists, like Dr. Lee, believed the question of concurrent versus sequential immunotherapy is “important.” But the field of oncology has an abundance of treatments that can now be aimed at a cancer, in a variety of potential combinations, they observed.
The editorialists concluded their commentary with a long list of needed work: “We should take this study to guide us to explore promising approaches in rigorous clinical trials, with a focus on sequential approaches such as definitive RT followed by immunotherapy, consolidative SBRT of all tumor sites in combination with immunotherapy, and trials that incorporate surrogate immunotherapy-relevant biomarkers to assess earlier and more efficiently the impact of an intervention.”
The study was partly supported by a grant from the National Cancer Institute. Bristol-Myers Squibb provided the study drug and funded tumor staining.
Multiple study authors have financial ties to industry, including two with ties to Bristol-Myers Squibb. Both editorialists have ties to industry, including Dr. Seiwert’s ties to Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
The phase 2, single-center study was conducted in 62 patients with head and neck cancer and at least two metastatic lesions. They were randomly assigned to receive nivolumab with or without additional radiation, delivered as stereotactic body radiation therapy (SBRT), but directed at only one of the metastatic lesions.
The results showed a similar rate of tumor shrinkage and disappearance in both groups (34.5% for nivolumab vs. 29.0% for the combination; P = .86) reported Sean McBride, MD, MPH, Memorial Sloan Kettering Cancer Center, New York, and colleagues in a paper published online in the Journal of Clinical Oncology.
The finding indicates that there was no abscopal effect, the team concluded.
The abscopal (from the Latin ab “away from” and scopus “target”) effect, first described in the 1950s, is a hypothetical result of radiation, whereby tumors situated outside the radiation field are reduced or eliminated by an assumed reaction mediated by the immune system.
This study is only the second randomized controlled trial to look at this effect. A previous trial in lung cancer (JAMA Oncol. 2019;5:1276) also failed to show a significant difference in objective response rate, the primary outcome.
In both studies, there was also no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of radiation.
“There are still die-hard proponents of the existence of an abscopal response, but it is clear from our data – there is no abscopal response,” lead study author Nancy Lee, MD, said in an interview.
Dr. Lee, also from Memorial Sloan Kettering, was referring to this trial in head and neck cancer specifically. But previous nonrandomized studies have also reported response rates for the combination of SBRT and immunotherapy that are similar to monotherapy, the authors point out. Overall, the collective data in oncology suggest that the abscopal response is “relatively rare,” the team comments.
A more emphatic statement comes from a pair of oncologists in an accompanying editorial.
The new study “provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare,” wrote Tanguy Seiwert, MD, medical oncologist, and Ana Kiess, MD, PhD, radiation oncologist, both at Johns Hopkins University, Baltimore.
This is a “well-executed study that has broader implications beyond head and neck cancer and speaks to larger issues of combination therapies in the era of cancer immunotherapy,” they also wrote.
The practice of using limited SBRT on any tumor type – along with anti–PD-1/PD-L1 therapy – “should not be pursued for the sole purpose of induction of an abscopal effect until we have better data to support any benefit,” the editorialists added.
It’s time to put the abscopal effect to rest, suggested Dr. Lee.
“Instead of focusing on whether an abscopal response exists or not, as it clearly did not in our phase 2 study, our focus should shift to the broader picture. What is the optimal timing of PD-1 or PD-L1 therapy in relation to radiotherapy?” she said.
The answer appears to be sequentially – and not concurrently, which is how radiation has been used to induce the would-be abscopal effect, she explained. “I personally feel that immunotherapy should not be given concurrently with radiation therapy.”
Damning data for the concurrent approach come from the phase 3 Javelin Head and Neck 100 trial, she said. In March, trial sponsors announced that the trial was terminated as it was unlikely to meet its primary endpoint. Specifically, adding an anti–PD-L1 therapy to chemoradiotherapy was not superior to chemoradiotherapy alone.
On the other hand, in the phase 3 lung cancer study known as PACIFIC, chemoradiotherapy followed by sequential anti–PD-L1 therapy showed “dramatic” improvements in PFS and OS, the editorialists pointed out.
Radiation and immunotherapy combinations
Despite the failure of this trial, radiation has “significant potential for combination with immunotherapy,” observed Dr. Seiwert and Dr. Kiess.
There are at least three potential roles of radiation therapy in combination with anti–PD-1/PD-L1 therapy, they wrote.
They explained that the first is single-site palliative radiation therapy/SBRT, which can control local symptoms. The second is “consolidation” of all tumor sites with radiation therapy/SBRT, which may decrease tumor burden and heterogeneity. And the third potential role is definitive locoregional radiation therapy to achieve long-term locoregional tumor control.
Thus, the editorialists, like Dr. Lee, believed the question of concurrent versus sequential immunotherapy is “important.” But the field of oncology has an abundance of treatments that can now be aimed at a cancer, in a variety of potential combinations, they observed.
The editorialists concluded their commentary with a long list of needed work: “We should take this study to guide us to explore promising approaches in rigorous clinical trials, with a focus on sequential approaches such as definitive RT followed by immunotherapy, consolidative SBRT of all tumor sites in combination with immunotherapy, and trials that incorporate surrogate immunotherapy-relevant biomarkers to assess earlier and more efficiently the impact of an intervention.”
The study was partly supported by a grant from the National Cancer Institute. Bristol-Myers Squibb provided the study drug and funded tumor staining.
Multiple study authors have financial ties to industry, including two with ties to Bristol-Myers Squibb. Both editorialists have ties to industry, including Dr. Seiwert’s ties to Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
The phase 2, single-center study was conducted in 62 patients with head and neck cancer and at least two metastatic lesions. They were randomly assigned to receive nivolumab with or without additional radiation, delivered as stereotactic body radiation therapy (SBRT), but directed at only one of the metastatic lesions.
The results showed a similar rate of tumor shrinkage and disappearance in both groups (34.5% for nivolumab vs. 29.0% for the combination; P = .86) reported Sean McBride, MD, MPH, Memorial Sloan Kettering Cancer Center, New York, and colleagues in a paper published online in the Journal of Clinical Oncology.
The finding indicates that there was no abscopal effect, the team concluded.
The abscopal (from the Latin ab “away from” and scopus “target”) effect, first described in the 1950s, is a hypothetical result of radiation, whereby tumors situated outside the radiation field are reduced or eliminated by an assumed reaction mediated by the immune system.
This study is only the second randomized controlled trial to look at this effect. A previous trial in lung cancer (JAMA Oncol. 2019;5:1276) also failed to show a significant difference in objective response rate, the primary outcome.
In both studies, there was also no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of radiation.
“There are still die-hard proponents of the existence of an abscopal response, but it is clear from our data – there is no abscopal response,” lead study author Nancy Lee, MD, said in an interview.
Dr. Lee, also from Memorial Sloan Kettering, was referring to this trial in head and neck cancer specifically. But previous nonrandomized studies have also reported response rates for the combination of SBRT and immunotherapy that are similar to monotherapy, the authors point out. Overall, the collective data in oncology suggest that the abscopal response is “relatively rare,” the team comments.
A more emphatic statement comes from a pair of oncologists in an accompanying editorial.
The new study “provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare,” wrote Tanguy Seiwert, MD, medical oncologist, and Ana Kiess, MD, PhD, radiation oncologist, both at Johns Hopkins University, Baltimore.
This is a “well-executed study that has broader implications beyond head and neck cancer and speaks to larger issues of combination therapies in the era of cancer immunotherapy,” they also wrote.
The practice of using limited SBRT on any tumor type – along with anti–PD-1/PD-L1 therapy – “should not be pursued for the sole purpose of induction of an abscopal effect until we have better data to support any benefit,” the editorialists added.
It’s time to put the abscopal effect to rest, suggested Dr. Lee.
“Instead of focusing on whether an abscopal response exists or not, as it clearly did not in our phase 2 study, our focus should shift to the broader picture. What is the optimal timing of PD-1 or PD-L1 therapy in relation to radiotherapy?” she said.
The answer appears to be sequentially – and not concurrently, which is how radiation has been used to induce the would-be abscopal effect, she explained. “I personally feel that immunotherapy should not be given concurrently with radiation therapy.”
Damning data for the concurrent approach come from the phase 3 Javelin Head and Neck 100 trial, she said. In March, trial sponsors announced that the trial was terminated as it was unlikely to meet its primary endpoint. Specifically, adding an anti–PD-L1 therapy to chemoradiotherapy was not superior to chemoradiotherapy alone.
On the other hand, in the phase 3 lung cancer study known as PACIFIC, chemoradiotherapy followed by sequential anti–PD-L1 therapy showed “dramatic” improvements in PFS and OS, the editorialists pointed out.
Radiation and immunotherapy combinations
Despite the failure of this trial, radiation has “significant potential for combination with immunotherapy,” observed Dr. Seiwert and Dr. Kiess.
There are at least three potential roles of radiation therapy in combination with anti–PD-1/PD-L1 therapy, they wrote.
They explained that the first is single-site palliative radiation therapy/SBRT, which can control local symptoms. The second is “consolidation” of all tumor sites with radiation therapy/SBRT, which may decrease tumor burden and heterogeneity. And the third potential role is definitive locoregional radiation therapy to achieve long-term locoregional tumor control.
Thus, the editorialists, like Dr. Lee, believed the question of concurrent versus sequential immunotherapy is “important.” But the field of oncology has an abundance of treatments that can now be aimed at a cancer, in a variety of potential combinations, they observed.
The editorialists concluded their commentary with a long list of needed work: “We should take this study to guide us to explore promising approaches in rigorous clinical trials, with a focus on sequential approaches such as definitive RT followed by immunotherapy, consolidative SBRT of all tumor sites in combination with immunotherapy, and trials that incorporate surrogate immunotherapy-relevant biomarkers to assess earlier and more efficiently the impact of an intervention.”
The study was partly supported by a grant from the National Cancer Institute. Bristol-Myers Squibb provided the study drug and funded tumor staining.
Multiple study authors have financial ties to industry, including two with ties to Bristol-Myers Squibb. Both editorialists have ties to industry, including Dr. Seiwert’s ties to Bristol-Myers Squibb.
A version of this article first appeared on Medscape.com.
FDA OKs first oral hormone therapy for advanced prostate cancer
Relugolix is an oral gonadotropin-releasing hormone antagonist. The new pill form may mean fewer clinic visits for patients, an added benefit during the COVID-19 pandemic, said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a press statement.
“Today’s approval marks the first oral drug in this class, and it may eliminate some patients’ need to visit the clinic for treatments that require administration by a health care provider,” he commented.
Relugolix works by preventing the pituitary gland from making luteinizing hormone and follicle-stimulating hormone, thus reducing the amount of testosterone the testicles can make.
In the open-label HERO trial, 930 patients with locally advanced or metastatic prostate cancer were randomly assigned to receive either once-daily oral relugolix or leuprolide injection every 3 months for 48 weeks.
The study met its primary endpoint, demonstrating that castration at 48 weeks was maintained in 96.7% of men receiving relugolix vs. 88.8% for patients receiving leuprolide; castration levels of testosterone had to be reached by day 29 and then sustained through the end of the treatment course.
Relugolix has the “potential to become a new standard for ADT and advanced prostate cancer,” commented study investigator Neal D. Shore, MD, of Carolina Urologic Research Center, Myrtle Beach, South Carolina, at the 2020 annual meeting of the American Society of Clinical Oncology, where the results were first presented.
They were published simultaneously in The New England Journal of Medicine.
At the ASCO meeting, David R. Wise, MD, PhD, Perlmutter Cancer Center at NYU Langone Health, New York, agreed that the drug could be practice-changing – but claimed that it would be for a subset of patients only, specifically, patients with a significant history of cardiovascular disease who are without gastrointestinal malabsorption.
Notably, in the study, relugolix cut the risk for major adverse cardiovascular events by 54% in comparison with leuprolide, as reported by Medscape Medical News.
According to the FDA, the most common side effects of relugolix include hot flush, increased glucose levels, increased triglyceride levels, musculoskeletal pain, decreased hemoglobin, fatigue, constipation, diarrhea, and increased levels of certain liver enzymes.
Concurrent use of relugolix with drugs that inhibit P-glycoprotein is contraindicated.
Also, health care providers should consider having patients undergo periodic electrocardiographic monitoring as well as periodic monitoring of electrolyte levels. Owing to the drug’s suppression of the pituitary gonadal system, any diagnostic test results of the pituitary gonadotropic and gonadal functions conducted during and after taking relugolix may be affected.
A version of this article first appeared on Medscape.com.
Relugolix is an oral gonadotropin-releasing hormone antagonist. The new pill form may mean fewer clinic visits for patients, an added benefit during the COVID-19 pandemic, said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a press statement.
“Today’s approval marks the first oral drug in this class, and it may eliminate some patients’ need to visit the clinic for treatments that require administration by a health care provider,” he commented.
Relugolix works by preventing the pituitary gland from making luteinizing hormone and follicle-stimulating hormone, thus reducing the amount of testosterone the testicles can make.
In the open-label HERO trial, 930 patients with locally advanced or metastatic prostate cancer were randomly assigned to receive either once-daily oral relugolix or leuprolide injection every 3 months for 48 weeks.
The study met its primary endpoint, demonstrating that castration at 48 weeks was maintained in 96.7% of men receiving relugolix vs. 88.8% for patients receiving leuprolide; castration levels of testosterone had to be reached by day 29 and then sustained through the end of the treatment course.
Relugolix has the “potential to become a new standard for ADT and advanced prostate cancer,” commented study investigator Neal D. Shore, MD, of Carolina Urologic Research Center, Myrtle Beach, South Carolina, at the 2020 annual meeting of the American Society of Clinical Oncology, where the results were first presented.
They were published simultaneously in The New England Journal of Medicine.
At the ASCO meeting, David R. Wise, MD, PhD, Perlmutter Cancer Center at NYU Langone Health, New York, agreed that the drug could be practice-changing – but claimed that it would be for a subset of patients only, specifically, patients with a significant history of cardiovascular disease who are without gastrointestinal malabsorption.
Notably, in the study, relugolix cut the risk for major adverse cardiovascular events by 54% in comparison with leuprolide, as reported by Medscape Medical News.
According to the FDA, the most common side effects of relugolix include hot flush, increased glucose levels, increased triglyceride levels, musculoskeletal pain, decreased hemoglobin, fatigue, constipation, diarrhea, and increased levels of certain liver enzymes.
Concurrent use of relugolix with drugs that inhibit P-glycoprotein is contraindicated.
Also, health care providers should consider having patients undergo periodic electrocardiographic monitoring as well as periodic monitoring of electrolyte levels. Owing to the drug’s suppression of the pituitary gonadal system, any diagnostic test results of the pituitary gonadotropic and gonadal functions conducted during and after taking relugolix may be affected.
A version of this article first appeared on Medscape.com.
Relugolix is an oral gonadotropin-releasing hormone antagonist. The new pill form may mean fewer clinic visits for patients, an added benefit during the COVID-19 pandemic, said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a press statement.
“Today’s approval marks the first oral drug in this class, and it may eliminate some patients’ need to visit the clinic for treatments that require administration by a health care provider,” he commented.
Relugolix works by preventing the pituitary gland from making luteinizing hormone and follicle-stimulating hormone, thus reducing the amount of testosterone the testicles can make.
In the open-label HERO trial, 930 patients with locally advanced or metastatic prostate cancer were randomly assigned to receive either once-daily oral relugolix or leuprolide injection every 3 months for 48 weeks.
The study met its primary endpoint, demonstrating that castration at 48 weeks was maintained in 96.7% of men receiving relugolix vs. 88.8% for patients receiving leuprolide; castration levels of testosterone had to be reached by day 29 and then sustained through the end of the treatment course.
Relugolix has the “potential to become a new standard for ADT and advanced prostate cancer,” commented study investigator Neal D. Shore, MD, of Carolina Urologic Research Center, Myrtle Beach, South Carolina, at the 2020 annual meeting of the American Society of Clinical Oncology, where the results were first presented.
They were published simultaneously in The New England Journal of Medicine.
At the ASCO meeting, David R. Wise, MD, PhD, Perlmutter Cancer Center at NYU Langone Health, New York, agreed that the drug could be practice-changing – but claimed that it would be for a subset of patients only, specifically, patients with a significant history of cardiovascular disease who are without gastrointestinal malabsorption.
Notably, in the study, relugolix cut the risk for major adverse cardiovascular events by 54% in comparison with leuprolide, as reported by Medscape Medical News.
According to the FDA, the most common side effects of relugolix include hot flush, increased glucose levels, increased triglyceride levels, musculoskeletal pain, decreased hemoglobin, fatigue, constipation, diarrhea, and increased levels of certain liver enzymes.
Concurrent use of relugolix with drugs that inhibit P-glycoprotein is contraindicated.
Also, health care providers should consider having patients undergo periodic electrocardiographic monitoring as well as periodic monitoring of electrolyte levels. Owing to the drug’s suppression of the pituitary gonadal system, any diagnostic test results of the pituitary gonadotropic and gonadal functions conducted during and after taking relugolix may be affected.
A version of this article first appeared on Medscape.com.