TBD Meeting (3035-21)

Lung cancer patients treated in community practices are not being comprehensively tested for biomarkers that could guide choice of first-line therapy, a recent retrospective analysis shows.

Less than half of patients with previously untreated non-small cell lung cancer (NSCLC) in a network of community practices underwent testing for all five biomarkers evaluated in the study, which was presented at the annual meeting of the American Society of Clinical Oncology (Abstract 9004).

Almost all of the 3,474 patients in the study (90%) had been tested for at least one biomarker, according to investigator Makenzi Colleen Evangelist, MD, an oncologist with New York Oncology Hematology, a practice in the US Oncology Network.

Only 46% were tested for all five biomarkers—ALK, BRAF, EGFR, ROS1, and PD-L1.

“While the proportion of patients tested for all five biomarkers increased over time, testing rates remain low at approximately 50%,” Dr. Evangelist said in a presentation of the results at the meeting.

This gap in testing illustrates “significant implementation challenges” that exist despite tremendous advances in biomarker-driven drug development and the technology to detect the mutations that can guide therapy, said Christine Marie Lovly, MD, PhD, the invited discussant for the study. “I would strongly argue that we have to apply what we already have to get equity, while still pushing the science forward,” said Dr. Lovly of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“We don’t want to miss the low-hanging fruit,” Dr. Lovly said. “We have to be able to make sure every patient with an EGFR mutation gets an EGFR tyrosine kinase inhibitor, and so forth, for all the other biomarkers that we test for.”
 

Real-world testing

The retrospective analysis of real-world biomarker testing patterns presented by Dr. Evangelist is the first of three protocols in the MYLUNG Consortium, a collaborative research study being conducted over a five-year period, according to the US Oncology Network.

The review of electronic health records included patients with metastatic NSCLC starting first-line systemic therapy between April 2018 and March 2020 in the US Oncology Network of community practices.

Rates of biomarker testing were highest for PD-L1, which was done for 83% of patients, the data show. EGFR and ALK testing were performed in 70% of patients, while ROS1 was evaluated in 68%. BRAF testing was done in 55% of patients. Testing rates appeared to be numerically higher for lung cancers with nonsquamous histology, according to Dr. Evangelist.

Over time, rates of specific biomarker testing were essentially unchanged, though a significant difference was seen for BRAF testing over time. BRAF was evaluated in 54% of patients starting therapy from April 2018 through September 2018, and 59%-62% in subsequent time periods (P = .005).

The proportion of patients tested for all five biomarkers was 44% in the April-September 2018 time period, and 50%-53% in subsequent time periods, the data show (P = .0056).

The proportion of patients tested with next-generation sequencing rose from 33% to 45% between 2018 and 2020, suggesting that comprehensive testing is increasing, according to Dr. Evangelist.

The turnaround time from testing orders to results was approximately 2 weeks, underscoring a need to get test results to oncologists sooner so they can consider biomarker data as they develop a treatment plan, the US Oncology Network said in a press release that described the study.

Median time from diagnosis to treatment in the study was approximately 5 weeks, which is “a concern for patients anxiously waiting for treatment,” the press release said.
 

Raising awareness

This study should serve to raise awareness that not all NSCLC patients who should be tested are being tested, study co-author Nicholas Robert, MD, said in an interview.

“There is a great line – ‘right drug, right patient, right time’ – and we’re not meeting that,” said Dr. Robert, vice president of medical affairs for Ontada, an oncology insights and technology company that is part of McKesson, which acquired the US Oncology Network in 2010.

The hope is that general oncologists will begin thinking of biomarker testing in NSCLC as being essential in the same way hormone receptor and HER2 testing are in breast cancer, according to Dr. Robert.

“You would never think about treating anyone with breast cancer without those variables,” he said. “We’d like to think that the general oncologist feels the same way about biomarkers in non-small cell cancer, that it’s something that should be done routinely across the board.”

The next phase of the MYLUNG Consortium study will prospectively evaluate biomarker test-ordering practices, turnaround times, and treatment decision making in approximately 1,000 patients from 11 sites, while the final phase will evaluate interventions to improve biomarker testing and access to therapies in up to 7,500 patients at 20 sites, according to the US Oncology Network.

Dr. Evangelist reported a consulting or advisory role with Takeda and AstraZeneca. Dr. Robert reported employment, leadership, and stock/ownership interest disclosures related to McKesson, along with other disclosures related to Johnson & Johnson, Oncolytics Biotech, Bristol-Myers Squibb, Roche, Advi, Boehringer Ingelheim, and New Century Health. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Lung cancer patients treated in community practices are not being comprehensively tested for biomarkers that could guide choice of first-line therapy, a recent retrospective analysis shows.

Less than half of patients with previously untreated non-small cell lung cancer (NSCLC) in a network of community practices underwent testing for all five biomarkers evaluated in the study, which was presented at the annual meeting of the American Society of Clinical Oncology (Abstract 9004).

Almost all of the 3,474 patients in the study (90%) had been tested for at least one biomarker, according to investigator Makenzi Colleen Evangelist, MD, an oncologist with New York Oncology Hematology, a practice in the US Oncology Network.

Only 46% were tested for all five biomarkers—ALK, BRAF, EGFR, ROS1, and PD-L1.

“While the proportion of patients tested for all five biomarkers increased over time, testing rates remain low at approximately 50%,” Dr. Evangelist said in a presentation of the results at the meeting.

This gap in testing illustrates “significant implementation challenges” that exist despite tremendous advances in biomarker-driven drug development and the technology to detect the mutations that can guide therapy, said Christine Marie Lovly, MD, PhD, the invited discussant for the study. “I would strongly argue that we have to apply what we already have to get equity, while still pushing the science forward,” said Dr. Lovly of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“We don’t want to miss the low-hanging fruit,” Dr. Lovly said. “We have to be able to make sure every patient with an EGFR mutation gets an EGFR tyrosine kinase inhibitor, and so forth, for all the other biomarkers that we test for.”
 

Real-world testing

The retrospective analysis of real-world biomarker testing patterns presented by Dr. Evangelist is the first of three protocols in the MYLUNG Consortium, a collaborative research study being conducted over a five-year period, according to the US Oncology Network.

The review of electronic health records included patients with metastatic NSCLC starting first-line systemic therapy between April 2018 and March 2020 in the US Oncology Network of community practices.

Rates of biomarker testing were highest for PD-L1, which was done for 83% of patients, the data show. EGFR and ALK testing were performed in 70% of patients, while ROS1 was evaluated in 68%. BRAF testing was done in 55% of patients. Testing rates appeared to be numerically higher for lung cancers with nonsquamous histology, according to Dr. Evangelist.

Over time, rates of specific biomarker testing were essentially unchanged, though a significant difference was seen for BRAF testing over time. BRAF was evaluated in 54% of patients starting therapy from April 2018 through September 2018, and 59%-62% in subsequent time periods (P = .005).

The proportion of patients tested for all five biomarkers was 44% in the April-September 2018 time period, and 50%-53% in subsequent time periods, the data show (P = .0056).

The proportion of patients tested with next-generation sequencing rose from 33% to 45% between 2018 and 2020, suggesting that comprehensive testing is increasing, according to Dr. Evangelist.

The turnaround time from testing orders to results was approximately 2 weeks, underscoring a need to get test results to oncologists sooner so they can consider biomarker data as they develop a treatment plan, the US Oncology Network said in a press release that described the study.

Median time from diagnosis to treatment in the study was approximately 5 weeks, which is “a concern for patients anxiously waiting for treatment,” the press release said.
 

Raising awareness

This study should serve to raise awareness that not all NSCLC patients who should be tested are being tested, study co-author Nicholas Robert, MD, said in an interview.

“There is a great line – ‘right drug, right patient, right time’ – and we’re not meeting that,” said Dr. Robert, vice president of medical affairs for Ontada, an oncology insights and technology company that is part of McKesson, which acquired the US Oncology Network in 2010.

The hope is that general oncologists will begin thinking of biomarker testing in NSCLC as being essential in the same way hormone receptor and HER2 testing are in breast cancer, according to Dr. Robert.

“You would never think about treating anyone with breast cancer without those variables,” he said. “We’d like to think that the general oncologist feels the same way about biomarkers in non-small cell cancer, that it’s something that should be done routinely across the board.”

The next phase of the MYLUNG Consortium study will prospectively evaluate biomarker test-ordering practices, turnaround times, and treatment decision making in approximately 1,000 patients from 11 sites, while the final phase will evaluate interventions to improve biomarker testing and access to therapies in up to 7,500 patients at 20 sites, according to the US Oncology Network.

Dr. Evangelist reported a consulting or advisory role with Takeda and AstraZeneca. Dr. Robert reported employment, leadership, and stock/ownership interest disclosures related to McKesson, along with other disclosures related to Johnson & Johnson, Oncolytics Biotech, Bristol-Myers Squibb, Roche, Advi, Boehringer Ingelheim, and New Century Health. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Lung cancer patients treated in community practices are not being comprehensively tested for biomarkers that could guide choice of first-line therapy, a recent retrospective analysis shows.

Less than half of patients with previously untreated non-small cell lung cancer (NSCLC) in a network of community practices underwent testing for all five biomarkers evaluated in the study, which was presented at the annual meeting of the American Society of Clinical Oncology (Abstract 9004).

Almost all of the 3,474 patients in the study (90%) had been tested for at least one biomarker, according to investigator Makenzi Colleen Evangelist, MD, an oncologist with New York Oncology Hematology, a practice in the US Oncology Network.

Only 46% were tested for all five biomarkers—ALK, BRAF, EGFR, ROS1, and PD-L1.

“While the proportion of patients tested for all five biomarkers increased over time, testing rates remain low at approximately 50%,” Dr. Evangelist said in a presentation of the results at the meeting.

This gap in testing illustrates “significant implementation challenges” that exist despite tremendous advances in biomarker-driven drug development and the technology to detect the mutations that can guide therapy, said Christine Marie Lovly, MD, PhD, the invited discussant for the study. “I would strongly argue that we have to apply what we already have to get equity, while still pushing the science forward,” said Dr. Lovly of the division of hematology-oncology at Vanderbilt University Medical Center in Nashville.

“We don’t want to miss the low-hanging fruit,” Dr. Lovly said. “We have to be able to make sure every patient with an EGFR mutation gets an EGFR tyrosine kinase inhibitor, and so forth, for all the other biomarkers that we test for.”
 

Real-world testing

The retrospective analysis of real-world biomarker testing patterns presented by Dr. Evangelist is the first of three protocols in the MYLUNG Consortium, a collaborative research study being conducted over a five-year period, according to the US Oncology Network.

The review of electronic health records included patients with metastatic NSCLC starting first-line systemic therapy between April 2018 and March 2020 in the US Oncology Network of community practices.

Rates of biomarker testing were highest for PD-L1, which was done for 83% of patients, the data show. EGFR and ALK testing were performed in 70% of patients, while ROS1 was evaluated in 68%. BRAF testing was done in 55% of patients. Testing rates appeared to be numerically higher for lung cancers with nonsquamous histology, according to Dr. Evangelist.

Over time, rates of specific biomarker testing were essentially unchanged, though a significant difference was seen for BRAF testing over time. BRAF was evaluated in 54% of patients starting therapy from April 2018 through September 2018, and 59%-62% in subsequent time periods (P = .005).

The proportion of patients tested for all five biomarkers was 44% in the April-September 2018 time period, and 50%-53% in subsequent time periods, the data show (P = .0056).

The proportion of patients tested with next-generation sequencing rose from 33% to 45% between 2018 and 2020, suggesting that comprehensive testing is increasing, according to Dr. Evangelist.

The turnaround time from testing orders to results was approximately 2 weeks, underscoring a need to get test results to oncologists sooner so they can consider biomarker data as they develop a treatment plan, the US Oncology Network said in a press release that described the study.

Median time from diagnosis to treatment in the study was approximately 5 weeks, which is “a concern for patients anxiously waiting for treatment,” the press release said.
 

Raising awareness

This study should serve to raise awareness that not all NSCLC patients who should be tested are being tested, study co-author Nicholas Robert, MD, said in an interview.

“There is a great line – ‘right drug, right patient, right time’ – and we’re not meeting that,” said Dr. Robert, vice president of medical affairs for Ontada, an oncology insights and technology company that is part of McKesson, which acquired the US Oncology Network in 2010.

The hope is that general oncologists will begin thinking of biomarker testing in NSCLC as being essential in the same way hormone receptor and HER2 testing are in breast cancer, according to Dr. Robert.

“You would never think about treating anyone with breast cancer without those variables,” he said. “We’d like to think that the general oncologist feels the same way about biomarkers in non-small cell cancer, that it’s something that should be done routinely across the board.”

The next phase of the MYLUNG Consortium study will prospectively evaluate biomarker test-ordering practices, turnaround times, and treatment decision making in approximately 1,000 patients from 11 sites, while the final phase will evaluate interventions to improve biomarker testing and access to therapies in up to 7,500 patients at 20 sites, according to the US Oncology Network.

Dr. Evangelist reported a consulting or advisory role with Takeda and AstraZeneca. Dr. Robert reported employment, leadership, and stock/ownership interest disclosures related to McKesson, along with other disclosures related to Johnson & Johnson, Oncolytics Biotech, Bristol-Myers Squibb, Roche, Advi, Boehringer Ingelheim, and New Century Health. Dr. Lovly reported disclosures related to Amgen, AstraZeneca, Genentech, Novartis, and Pfizer, among others.

Experiencing an immune-related adverse event during checkpoint inhibitor treatment may predict outcomes in patients with non-small cell lung cancer, exploratory analyses of phase 3 trials suggest.

Immune-related adverse events (irAEs) were tied to longer overall survival (OS) in exploratory pooled analyses of three phase 3 clinical trials evaluating atezolizumab-based regimens, according to investigator Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, Fla.

Median OS approached 26 months for patients who received first-line atezolizumab and experienced an irAE, compared with just 13 months for those who did not experience an irAE, according to results reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9002).

Atezolizumab-treated patients with grade 3 or greater irAEs had the shortest OS, shorter than those atezolizumab-treated patients who experienced grade 1-2 irAEs or no irAEs at all. That short OS may be due to treatment interruptions or discontinuations, said Dr. Socinski.

“Data from these analyses suggest an association between irAEs and efficacy in patients with [non-small cell cancer] NSCLC,” he stated in his presentation of the results.
 

A lot more to learn about irAEs

Similar linkages between irAEs and outcomes were observed in pooled analyses of patients enrolled in the control arms of the phase 3 trials, with a median OS of about 20 months for control patients experiencing an irAE, versus about 13 months for those who did not.

That linkage in the control arm prompted a question from an ASCO attendee about why an effect of irAEs, commonly associated with immune checkpoint inhibitor therapy, would be evident in analyses of patients who did not receive those agents.

In his response, Dr. Socinski characterized the finding as “a surprise” and said the finding may either reflect how adverse events are characterized or how chemotherapy impacts the immune system.

“I don’t know that our definition of irAEs is perfect,” he said, “and maybe we don’t understand what impact chemotherapy may have on the immune system, and may actually engender what historically we’ve always seen as an adverse event, but didn’t necessarily classify as an immune-related adverse event.”

More work is needed to better understand the connection between irAES and outcomes, and whether anything can be done as a result of that improved understanding, said discussant Mary Weber Redman, PhD.

“The question is, ‘what is actionable?’” added Dr. Redman, a biostatistician at the Fred Hutchinson Cancer Research Center, Seattle.

A firmer understanding of the relationship between irAEs and outcomes could change how clinicians monitor patients for irAEs, lead to better prediction of which patients may experience higher grade irAEs, and ultimately impact treatment selection potentially to avoid those higher grade events, Dr. Redman said in her remarks.

“Doing these types of analyses are quite important, because we have to look at the breadth of information that we have to be able to interpret that and think about what are future questions,” she said in the question-and-answer session accompanying Dr. Socinski’s presentation.

“I think the key is that we shouldn’t use these analyses to be definitive, but we should use them as to be hypothesis generating,” she added.
 

More evidence to link irAEs and outcomes

Immune-related AEs caused by off-target immune and inflammatory activity have been reported in up to 80% of patients receiving immune checkpoint inhibitors as monotherapy and up to 95% in combination regimens, Dr. Socinski said in his presentation.

“Increasing evidence suggests that the occurrence of immune-related adverse events with PD-L1 or PD-1 inhibitor therapy may be predictive of improved outcomes in cancers such as NSCLC, “ he added.

In their exploratory pooled analyses, Dr. Socinski and co-investigators looked at data from the phase 3 IMpower130 and IMpower132 trials, which evaluated first-line atezolizumab and chemotherapy for NSCLC, and the phase 3 IMpower150 trial, which evaluated atezolizumab plus chemotherapy with or without bevacizumab.

In all, they analyzed data for 1,557 atezolizumab-treated patients, and 900 patients who had been in the control arms of the studies.

Forty-eight percent of atezolizumab-treated patients experienced irAEs of any grade, while 11% experienced irAEs of grade 3-5, according to the presented data. In the control arm, 32% experienced irAEs of any grade and 5% experienced grade 3-5 irAEs.

The most common irAEs of any grade were rash, hepatitis, and hypothyroidism, occurring in 28%, 15%, and 12% of atezolizumab-treated patients, respectively.

Median OS in the atezolizumab arm was 25.7 months for patients with irAEs and 13.0 for patients with no irAEs, with a hazard ratio (HR) of 0.69 using a time-dependent Cox model.

Median OS in the control arm was 20.2 months for patients with irAEs and 12.8 months for patients with no irAEs, with an HR of 0.82.

The overall response rate (ORR) in the atezolizumab arm was 61.1% for patients with irAEs and 37.2% for those without irAEs; in the control arm, ORR was 42.2% for patients with irAEs and 34.0% for those with no irAEs.

Atezolizumab-treated patients who experienced grade 3-5 irAEs had the shortest OS, according to Dr. Socinski. The HRs for OS at 1, 3, 6, and 12 months in atezolizumab-treated patients with grade 3-5 irAEs (compared with those without irAEs) ranged from 1.25 to 0.87. By contrast, HRs at those time points for patients with grade 1-2 irAEs ranged from 0.78 to 0.72, Dr. Socinski said.

Dr. Socinski reported disclosures related to AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Guardant Health, Janssen, Lilly, Merck, Novartis, Roche/Genentech, and Spectrum Pharmaceuticals. Dr. Redman reported a consulting or advisory role with AstraZeneca.

Experiencing an immune-related adverse event during checkpoint inhibitor treatment may predict outcomes in patients with non-small cell lung cancer, exploratory analyses of phase 3 trials suggest.

Immune-related adverse events (irAEs) were tied to longer overall survival (OS) in exploratory pooled analyses of three phase 3 clinical trials evaluating atezolizumab-based regimens, according to investigator Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, Fla.

Median OS approached 26 months for patients who received first-line atezolizumab and experienced an irAE, compared with just 13 months for those who did not experience an irAE, according to results reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9002).

Atezolizumab-treated patients with grade 3 or greater irAEs had the shortest OS, shorter than those atezolizumab-treated patients who experienced grade 1-2 irAEs or no irAEs at all. That short OS may be due to treatment interruptions or discontinuations, said Dr. Socinski.

“Data from these analyses suggest an association between irAEs and efficacy in patients with [non-small cell cancer] NSCLC,” he stated in his presentation of the results.
 

A lot more to learn about irAEs

Similar linkages between irAEs and outcomes were observed in pooled analyses of patients enrolled in the control arms of the phase 3 trials, with a median OS of about 20 months for control patients experiencing an irAE, versus about 13 months for those who did not.

That linkage in the control arm prompted a question from an ASCO attendee about why an effect of irAEs, commonly associated with immune checkpoint inhibitor therapy, would be evident in analyses of patients who did not receive those agents.

In his response, Dr. Socinski characterized the finding as “a surprise” and said the finding may either reflect how adverse events are characterized or how chemotherapy impacts the immune system.

“I don’t know that our definition of irAEs is perfect,” he said, “and maybe we don’t understand what impact chemotherapy may have on the immune system, and may actually engender what historically we’ve always seen as an adverse event, but didn’t necessarily classify as an immune-related adverse event.”

More work is needed to better understand the connection between irAES and outcomes, and whether anything can be done as a result of that improved understanding, said discussant Mary Weber Redman, PhD.

“The question is, ‘what is actionable?’” added Dr. Redman, a biostatistician at the Fred Hutchinson Cancer Research Center, Seattle.

A firmer understanding of the relationship between irAEs and outcomes could change how clinicians monitor patients for irAEs, lead to better prediction of which patients may experience higher grade irAEs, and ultimately impact treatment selection potentially to avoid those higher grade events, Dr. Redman said in her remarks.

“Doing these types of analyses are quite important, because we have to look at the breadth of information that we have to be able to interpret that and think about what are future questions,” she said in the question-and-answer session accompanying Dr. Socinski’s presentation.

“I think the key is that we shouldn’t use these analyses to be definitive, but we should use them as to be hypothesis generating,” she added.
 

More evidence to link irAEs and outcomes

Immune-related AEs caused by off-target immune and inflammatory activity have been reported in up to 80% of patients receiving immune checkpoint inhibitors as monotherapy and up to 95% in combination regimens, Dr. Socinski said in his presentation.

“Increasing evidence suggests that the occurrence of immune-related adverse events with PD-L1 or PD-1 inhibitor therapy may be predictive of improved outcomes in cancers such as NSCLC, “ he added.

In their exploratory pooled analyses, Dr. Socinski and co-investigators looked at data from the phase 3 IMpower130 and IMpower132 trials, which evaluated first-line atezolizumab and chemotherapy for NSCLC, and the phase 3 IMpower150 trial, which evaluated atezolizumab plus chemotherapy with or without bevacizumab.

In all, they analyzed data for 1,557 atezolizumab-treated patients, and 900 patients who had been in the control arms of the studies.

Forty-eight percent of atezolizumab-treated patients experienced irAEs of any grade, while 11% experienced irAEs of grade 3-5, according to the presented data. In the control arm, 32% experienced irAEs of any grade and 5% experienced grade 3-5 irAEs.

The most common irAEs of any grade were rash, hepatitis, and hypothyroidism, occurring in 28%, 15%, and 12% of atezolizumab-treated patients, respectively.

Median OS in the atezolizumab arm was 25.7 months for patients with irAEs and 13.0 for patients with no irAEs, with a hazard ratio (HR) of 0.69 using a time-dependent Cox model.

Median OS in the control arm was 20.2 months for patients with irAEs and 12.8 months for patients with no irAEs, with an HR of 0.82.

The overall response rate (ORR) in the atezolizumab arm was 61.1% for patients with irAEs and 37.2% for those without irAEs; in the control arm, ORR was 42.2% for patients with irAEs and 34.0% for those with no irAEs.

Atezolizumab-treated patients who experienced grade 3-5 irAEs had the shortest OS, according to Dr. Socinski. The HRs for OS at 1, 3, 6, and 12 months in atezolizumab-treated patients with grade 3-5 irAEs (compared with those without irAEs) ranged from 1.25 to 0.87. By contrast, HRs at those time points for patients with grade 1-2 irAEs ranged from 0.78 to 0.72, Dr. Socinski said.

Dr. Socinski reported disclosures related to AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Guardant Health, Janssen, Lilly, Merck, Novartis, Roche/Genentech, and Spectrum Pharmaceuticals. Dr. Redman reported a consulting or advisory role with AstraZeneca.

Experiencing an immune-related adverse event during checkpoint inhibitor treatment may predict outcomes in patients with non-small cell lung cancer, exploratory analyses of phase 3 trials suggest.

Immune-related adverse events (irAEs) were tied to longer overall survival (OS) in exploratory pooled analyses of three phase 3 clinical trials evaluating atezolizumab-based regimens, according to investigator Mark A. Socinski, MD, of AdventHealth Cancer Institute, Orlando, Fla.

Median OS approached 26 months for patients who received first-line atezolizumab and experienced an irAE, compared with just 13 months for those who did not experience an irAE, according to results reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9002).

Atezolizumab-treated patients with grade 3 or greater irAEs had the shortest OS, shorter than those atezolizumab-treated patients who experienced grade 1-2 irAEs or no irAEs at all. That short OS may be due to treatment interruptions or discontinuations, said Dr. Socinski.

“Data from these analyses suggest an association between irAEs and efficacy in patients with [non-small cell cancer] NSCLC,” he stated in his presentation of the results.
 

A lot more to learn about irAEs

Similar linkages between irAEs and outcomes were observed in pooled analyses of patients enrolled in the control arms of the phase 3 trials, with a median OS of about 20 months for control patients experiencing an irAE, versus about 13 months for those who did not.

That linkage in the control arm prompted a question from an ASCO attendee about why an effect of irAEs, commonly associated with immune checkpoint inhibitor therapy, would be evident in analyses of patients who did not receive those agents.

In his response, Dr. Socinski characterized the finding as “a surprise” and said the finding may either reflect how adverse events are characterized or how chemotherapy impacts the immune system.

“I don’t know that our definition of irAEs is perfect,” he said, “and maybe we don’t understand what impact chemotherapy may have on the immune system, and may actually engender what historically we’ve always seen as an adverse event, but didn’t necessarily classify as an immune-related adverse event.”

More work is needed to better understand the connection between irAES and outcomes, and whether anything can be done as a result of that improved understanding, said discussant Mary Weber Redman, PhD.

“The question is, ‘what is actionable?’” added Dr. Redman, a biostatistician at the Fred Hutchinson Cancer Research Center, Seattle.

A firmer understanding of the relationship between irAEs and outcomes could change how clinicians monitor patients for irAEs, lead to better prediction of which patients may experience higher grade irAEs, and ultimately impact treatment selection potentially to avoid those higher grade events, Dr. Redman said in her remarks.

“Doing these types of analyses are quite important, because we have to look at the breadth of information that we have to be able to interpret that and think about what are future questions,” she said in the question-and-answer session accompanying Dr. Socinski’s presentation.

“I think the key is that we shouldn’t use these analyses to be definitive, but we should use them as to be hypothesis generating,” she added.
 

More evidence to link irAEs and outcomes

Immune-related AEs caused by off-target immune and inflammatory activity have been reported in up to 80% of patients receiving immune checkpoint inhibitors as monotherapy and up to 95% in combination regimens, Dr. Socinski said in his presentation.

“Increasing evidence suggests that the occurrence of immune-related adverse events with PD-L1 or PD-1 inhibitor therapy may be predictive of improved outcomes in cancers such as NSCLC, “ he added.

In their exploratory pooled analyses, Dr. Socinski and co-investigators looked at data from the phase 3 IMpower130 and IMpower132 trials, which evaluated first-line atezolizumab and chemotherapy for NSCLC, and the phase 3 IMpower150 trial, which evaluated atezolizumab plus chemotherapy with or without bevacizumab.

In all, they analyzed data for 1,557 atezolizumab-treated patients, and 900 patients who had been in the control arms of the studies.

Forty-eight percent of atezolizumab-treated patients experienced irAEs of any grade, while 11% experienced irAEs of grade 3-5, according to the presented data. In the control arm, 32% experienced irAEs of any grade and 5% experienced grade 3-5 irAEs.

The most common irAEs of any grade were rash, hepatitis, and hypothyroidism, occurring in 28%, 15%, and 12% of atezolizumab-treated patients, respectively.

Median OS in the atezolizumab arm was 25.7 months for patients with irAEs and 13.0 for patients with no irAEs, with a hazard ratio (HR) of 0.69 using a time-dependent Cox model.

Median OS in the control arm was 20.2 months for patients with irAEs and 12.8 months for patients with no irAEs, with an HR of 0.82.

The overall response rate (ORR) in the atezolizumab arm was 61.1% for patients with irAEs and 37.2% for those without irAEs; in the control arm, ORR was 42.2% for patients with irAEs and 34.0% for those with no irAEs.

Atezolizumab-treated patients who experienced grade 3-5 irAEs had the shortest OS, according to Dr. Socinski. The HRs for OS at 1, 3, 6, and 12 months in atezolizumab-treated patients with grade 3-5 irAEs (compared with those without irAEs) ranged from 1.25 to 0.87. By contrast, HRs at those time points for patients with grade 1-2 irAEs ranged from 0.78 to 0.72, Dr. Socinski said.

Dr. Socinski reported disclosures related to AstraZeneca/MedImmune, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech, Guardant Health, Janssen, Lilly, Merck, Novartis, Roche/Genentech, and Spectrum Pharmaceuticals. Dr. Redman reported a consulting or advisory role with AstraZeneca.

The higher the HER2 expression, the more benefit patients get from the antibody-drug conjugate trastuzumab deruxtecan (Enhertu) for HER2-positive metastatic colorectal cancer in the salvage setting, according to a phase 2 report.

Among the 53 patients with the highest expression in the study – defined as 3+ expression on immune histochemical staining or 2+ with positive in situ hybridization – median progression median progression-free survival (mPFS) was 6.9 months after failure of a median of four prior regimens.

With standard drugs, mPFS would be expected to be about 2 months or less, said investigator Kanwal Pratap Singh Raghav, MD, an associate professor of GI medical oncology at MD Anderson Cancer Center, Houston.

Many of the 86 study participants were enrolled at MD Anderson, and “they all derived some benefit from the conjugate. “It’s fairly well tolerated,” and “our experience has been pretty good; I think it’s actually a pretty good drug,” Dr. Raghav said shortly before presenting the findings at the American Society of Clinical Oncology Annual Meeting.

HER2 is over-expressed in about 5% of colorectal cancer patients. The conjugate is a kind of “smart bomb” for them that combines the anti-HER2 antibody trastuzumab (Herceptin) with a potent topoisomerase I inhibitor. The trastuzumab portion of the combination zeros in on cancer cells expressing HER2, delivering the cytotoxic agent directly to them.

“The amount of [cytotoxic] drug delivered by the antibody inside the cell is far in excess” to the standard approach of delivering chemotherapy agents individually, Dr. Raghav said.

“Single-agent treatments targeting HER2 only have modest activity. Seeing a response rate of [almost] 50% in colorectal cancer tumors that have high expression of HER2 is very exciting,” Muhammad Beg, MD, a GI oncologist and associate professor at UT Southwestern Medical Center, Dallas, said when asked for comment.

Trastuzumab deruxtecan already is approved for metastatic HER2-positive breast cancer after at least two anti-HER2-based regimens and locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma after a prior trastuzumab-based regime.

The phase 2 study, dubbed DESTINY-CRC01, divided patients by HER2 expression. In addition to the 53 “high-expressors,” there were 15 medium-expressors – defined as 2+ on immunohistochemical staining and no in situ hybridization – and 18 low-expressors with 1+ HER2 expression.

The patients had run out of other options, having experienced progression on 2 to 11 previous regimens. All participants had been on the topoisomerase I inhibitor irinotecan before, and almost a third of the high-expressors had been on anti-HER2 regimen.

They were treated with 6.4 mg/kg trastuzumab deruxtecan every 3 weeks for a median of 3 months. There was no control group.

The overall response rate was 45.3% among high-expressors. In addition to the mPFS of 6.9 months, median overall survival was 15.5 months. Among those on prior anti-HER2 therapy, the overall response rate was 43.8%.

Benefit was minimal in the lower-expression groups, with a mPFS of 2.1 months and overall survival of 7.3 months in medium-expressors and a mPFS of 1.4 months and overall survival of 7.7 months in low-expressors.

Sixty-five percent of patients (56) had treatment-emergent grade 3 or worse adverse events, most commonly hematologic and gastrointestinal; 13 subjects (15.1%) discontinued due to adverse events.

Eight patients (9.3%) developed interstitial lung disease, a particular concern with trastuzumab deruxtecan; it was fatal for three. “We need to study the lung toxicity. It will become a bigger factor as we think about using this drug for earlier lines of treatment,” Dr. Beg noted.

The median age in the study was 58.5 years, just over half the subjects were men, and more than 90% had left-sided colon or rectum cancer.

The next step in development is a randomized trial in unresectable/metastatic HER2-positive colorectal cancer dubbed DESTINY-CRC02, comparing the 6.4 mg dose with 5.4 mg. It’s already started recruiting.

The work was funded by trastuzumab deruxtecan maker Daiichi Sankyo. Dr. Raghav is an advisor and researcher for the company; Dr. Beg had no relationships with it.

aotto@mdedge.com

The higher the HER2 expression, the more benefit patients get from the antibody-drug conjugate trastuzumab deruxtecan (Enhertu) for HER2-positive metastatic colorectal cancer in the salvage setting, according to a phase 2 report.

Among the 53 patients with the highest expression in the study – defined as 3+ expression on immune histochemical staining or 2+ with positive in situ hybridization – median progression median progression-free survival (mPFS) was 6.9 months after failure of a median of four prior regimens.

With standard drugs, mPFS would be expected to be about 2 months or less, said investigator Kanwal Pratap Singh Raghav, MD, an associate professor of GI medical oncology at MD Anderson Cancer Center, Houston.

Many of the 86 study participants were enrolled at MD Anderson, and “they all derived some benefit from the conjugate. “It’s fairly well tolerated,” and “our experience has been pretty good; I think it’s actually a pretty good drug,” Dr. Raghav said shortly before presenting the findings at the American Society of Clinical Oncology Annual Meeting.

HER2 is over-expressed in about 5% of colorectal cancer patients. The conjugate is a kind of “smart bomb” for them that combines the anti-HER2 antibody trastuzumab (Herceptin) with a potent topoisomerase I inhibitor. The trastuzumab portion of the combination zeros in on cancer cells expressing HER2, delivering the cytotoxic agent directly to them.

“The amount of [cytotoxic] drug delivered by the antibody inside the cell is far in excess” to the standard approach of delivering chemotherapy agents individually, Dr. Raghav said.

“Single-agent treatments targeting HER2 only have modest activity. Seeing a response rate of [almost] 50% in colorectal cancer tumors that have high expression of HER2 is very exciting,” Muhammad Beg, MD, a GI oncologist and associate professor at UT Southwestern Medical Center, Dallas, said when asked for comment.

Trastuzumab deruxtecan already is approved for metastatic HER2-positive breast cancer after at least two anti-HER2-based regimens and locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma after a prior trastuzumab-based regime.

The phase 2 study, dubbed DESTINY-CRC01, divided patients by HER2 expression. In addition to the 53 “high-expressors,” there were 15 medium-expressors – defined as 2+ on immunohistochemical staining and no in situ hybridization – and 18 low-expressors with 1+ HER2 expression.

The patients had run out of other options, having experienced progression on 2 to 11 previous regimens. All participants had been on the topoisomerase I inhibitor irinotecan before, and almost a third of the high-expressors had been on anti-HER2 regimen.

They were treated with 6.4 mg/kg trastuzumab deruxtecan every 3 weeks for a median of 3 months. There was no control group.

The overall response rate was 45.3% among high-expressors. In addition to the mPFS of 6.9 months, median overall survival was 15.5 months. Among those on prior anti-HER2 therapy, the overall response rate was 43.8%.

Benefit was minimal in the lower-expression groups, with a mPFS of 2.1 months and overall survival of 7.3 months in medium-expressors and a mPFS of 1.4 months and overall survival of 7.7 months in low-expressors.

Sixty-five percent of patients (56) had treatment-emergent grade 3 or worse adverse events, most commonly hematologic and gastrointestinal; 13 subjects (15.1%) discontinued due to adverse events.

Eight patients (9.3%) developed interstitial lung disease, a particular concern with trastuzumab deruxtecan; it was fatal for three. “We need to study the lung toxicity. It will become a bigger factor as we think about using this drug for earlier lines of treatment,” Dr. Beg noted.

The median age in the study was 58.5 years, just over half the subjects were men, and more than 90% had left-sided colon or rectum cancer.

The next step in development is a randomized trial in unresectable/metastatic HER2-positive colorectal cancer dubbed DESTINY-CRC02, comparing the 6.4 mg dose with 5.4 mg. It’s already started recruiting.

The work was funded by trastuzumab deruxtecan maker Daiichi Sankyo. Dr. Raghav is an advisor and researcher for the company; Dr. Beg had no relationships with it.

aotto@mdedge.com

The higher the HER2 expression, the more benefit patients get from the antibody-drug conjugate trastuzumab deruxtecan (Enhertu) for HER2-positive metastatic colorectal cancer in the salvage setting, according to a phase 2 report.

Among the 53 patients with the highest expression in the study – defined as 3+ expression on immune histochemical staining or 2+ with positive in situ hybridization – median progression median progression-free survival (mPFS) was 6.9 months after failure of a median of four prior regimens.

With standard drugs, mPFS would be expected to be about 2 months or less, said investigator Kanwal Pratap Singh Raghav, MD, an associate professor of GI medical oncology at MD Anderson Cancer Center, Houston.

Many of the 86 study participants were enrolled at MD Anderson, and “they all derived some benefit from the conjugate. “It’s fairly well tolerated,” and “our experience has been pretty good; I think it’s actually a pretty good drug,” Dr. Raghav said shortly before presenting the findings at the American Society of Clinical Oncology Annual Meeting.

HER2 is over-expressed in about 5% of colorectal cancer patients. The conjugate is a kind of “smart bomb” for them that combines the anti-HER2 antibody trastuzumab (Herceptin) with a potent topoisomerase I inhibitor. The trastuzumab portion of the combination zeros in on cancer cells expressing HER2, delivering the cytotoxic agent directly to them.

“The amount of [cytotoxic] drug delivered by the antibody inside the cell is far in excess” to the standard approach of delivering chemotherapy agents individually, Dr. Raghav said.

“Single-agent treatments targeting HER2 only have modest activity. Seeing a response rate of [almost] 50% in colorectal cancer tumors that have high expression of HER2 is very exciting,” Muhammad Beg, MD, a GI oncologist and associate professor at UT Southwestern Medical Center, Dallas, said when asked for comment.

Trastuzumab deruxtecan already is approved for metastatic HER2-positive breast cancer after at least two anti-HER2-based regimens and locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma after a prior trastuzumab-based regime.

The phase 2 study, dubbed DESTINY-CRC01, divided patients by HER2 expression. In addition to the 53 “high-expressors,” there were 15 medium-expressors – defined as 2+ on immunohistochemical staining and no in situ hybridization – and 18 low-expressors with 1+ HER2 expression.

The patients had run out of other options, having experienced progression on 2 to 11 previous regimens. All participants had been on the topoisomerase I inhibitor irinotecan before, and almost a third of the high-expressors had been on anti-HER2 regimen.

They were treated with 6.4 mg/kg trastuzumab deruxtecan every 3 weeks for a median of 3 months. There was no control group.

The overall response rate was 45.3% among high-expressors. In addition to the mPFS of 6.9 months, median overall survival was 15.5 months. Among those on prior anti-HER2 therapy, the overall response rate was 43.8%.

Benefit was minimal in the lower-expression groups, with a mPFS of 2.1 months and overall survival of 7.3 months in medium-expressors and a mPFS of 1.4 months and overall survival of 7.7 months in low-expressors.

Sixty-five percent of patients (56) had treatment-emergent grade 3 or worse adverse events, most commonly hematologic and gastrointestinal; 13 subjects (15.1%) discontinued due to adverse events.

Eight patients (9.3%) developed interstitial lung disease, a particular concern with trastuzumab deruxtecan; it was fatal for three. “We need to study the lung toxicity. It will become a bigger factor as we think about using this drug for earlier lines of treatment,” Dr. Beg noted.

The median age in the study was 58.5 years, just over half the subjects were men, and more than 90% had left-sided colon or rectum cancer.

The next step in development is a randomized trial in unresectable/metastatic HER2-positive colorectal cancer dubbed DESTINY-CRC02, comparing the 6.4 mg dose with 5.4 mg. It’s already started recruiting.

The work was funded by trastuzumab deruxtecan maker Daiichi Sankyo. Dr. Raghav is an advisor and researcher for the company; Dr. Beg had no relationships with it.

aotto@mdedge.com

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

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

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

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

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

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

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

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

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

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

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

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

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

Immunotherapy has already had a huge impact on treatment of patients with later stages of non–small cell lung cancer (NSCLC): new clinical data are now showing benefits in patients with earlier stage disease.

Patients with stage IB-IIIA NSCLC showed a markedly improved disease-free survival (DFS) when atezolizumab (Tecentriq) was added onto adjuvant chemotherapy following resection, according to results from an interim analysis of the IMpower010 study.

Notably, the benefit with atezolizumab versus best supportive care was greatest in patients with expression of programmed death–ligand 1 (PD-L1) on their tumor, in whom the DFS improvement was a significant 34%.

This is the “first global phase 3 trial using an immune checkpoint inhibitor to show a disease-free survival outcome in early-stage NSCLC,” said lead researcher Heather Wakelee, MD, professor of medicine and chief of the division of oncology at Stanford (Calif.) University Medical Center.

She was speaking at a press briefing ahead of the American Society of Clinical Oncology annual meeting, where the results will be presented on June 6.

Dr. Wakelee added that the “planned analysis for disease-free survival and overall survival in the intention-to-treat populations will continue with longer-term follow-up.”

Asked whether the drug could be recommended for these patients based on the current results, Dr. Wakelee said that “obviously we need approval” for this use from the Food and Drug Administration, but she added that “the FDA has approved other agents, particularly most recently osimertinib [Tagrisso], based on a disease-free survival endpoint.”

These new results show that the benefit with atezolizumab plus chemotherapy is “more profound” than with chemotherapy plus best supportive care, “and therefore, to me, it would be something I would want to offer my patients in that setting.”

Dr. Wakelee also emphasized the importance of screening for lung cancer, so that the disease is detected at earlier stages “when it is potentially curable.”

She also stressed the importance of biomarker testing for patients with resected disease “to look for EGFR mutations, which can be treated with EGFR [tyrosine kinase inhibitors] and also, at some point, to check for PD-L1 ... because, in this trial, the vast majority of benefit” appeared to be in those with PD-L1 expression on their tumors.

Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, said that “immune checkpoint inhibitors have certainly changed the treatment landscape for many types of cancers” and the current study “is the first time we’ve seen an immunotherapy that’s effective in treating early-stage NSCLC.”

“This is an important advance in understanding the role of immunotherapy in earlier stage lung cancer” and “potentially a step forward for many patients.”
 

Study details 

The standard of care for many stage IB-IIIA NSCLC patients “has not changed for many years,” despite “significant progress” having been made in the treatment of more advanced disease, Dr. Wakelee commented.

Consequently, the majority of patients with resected NSCLC continue to receive adjuvant platinum-based chemotherapy, which has been shown to reduce the risk of disease recurrence by 16% in those with completely resected disease.

The new study set out to examine the benefit of adding atezolizumab to adjuvant chemotherapy in the global phase 3 IMpower010 study.

Patients had to have stage IB-IIIA NSCLC, with stage IB tumors at least 4 cm in size, and tumor tissue available for PD-L1 analysis. Following complete resection, 1,280 patients were given up to four cycles of adjuvant platinum-based chemotherapy.

Of those, 1,005 patients were then randomly assigned 1:1 to receive either 16 cycles of atezolizumab 1,200 mg IV every 3 weeks or best supportive care.

The interim results show that, after a median follow-up of 32.8 months, the addition of atezolizumab significantly reduced the risk of recurrence or death versus best supportive care in patients whose tumors had PD-L1 expression of at least 1%, at a hazard ratio of 0.66 (P = .004).

At 24 months, the DFS rate was 74.6% among patients given atezolizumab versus 61% in those receiving best supportive care, reducing to 60% and 48.2%, respectively, at 36 months.

When looking across all randomized patients, the addition of atezolizumab was associated with a smaller reduction in the risk of recurrence of death versus best supportive care, at a hazard ratio of 0.79 after a median follow-up of 32.2 months (P = .02).

On the intention to treat analysis, the reduction in the risk of recurrence or death with atezolizumab was of borderline significance, at a hazard ratio of 0.81 after a median follow-up of 32.2 months (P = .04).

Dr. Wakelee pointed out that patients with stage IB disease, who represented around 12% of those in the trial, “tend to do better and we require longer time to see some of the disease recurrence outcomes,” and so these results are “preliminary.”

She also emphasized that the overall survival data are not yet mature and survival was not formally tested in the current analysis.

In terms of safety, the adverse event profile with atezolizumab was consistent with previous reports, the investigators noted in the abstract. However, Dr. Wakelee said at the briefing that “we had to stop treatment with atezolizumab in 18% of patients because of toxicity.”

All-grade adverse events were reported in 70.7% of the best supportive care group versus 92.7% among those given atezolizumab, while grade 3-4 adverse events were reported in 11.5% and 21.8% of patients, respectively.

The study was funded by Hoffmann–La Roche. Dr. Wakelee reported relationships with AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Helsinn Therapeutics, Janssen Oncology, Mirati Therapeutics, Xcovery, ACEA Biosciences, Arrys Therapeutics, AstraZeneca/MedImmune, Bristol-Myers Squibb, Celgene, Clovis Oncology, Exelixis, Genentech/Roche, Gilead Sciences, Merck, Novartis, Pharmacyclics, Seattle Genetics, and Xcovery. She also reports uncompensated relationships with Genentech/Roche, Merck, and Takeda. Dr. Gralow reported relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Immunotherapy has already had a huge impact on treatment of patients with later stages of non–small cell lung cancer (NSCLC): new clinical data are now showing benefits in patients with earlier stage disease.

Patients with stage IB-IIIA NSCLC showed a markedly improved disease-free survival (DFS) when atezolizumab (Tecentriq) was added onto adjuvant chemotherapy following resection, according to results from an interim analysis of the IMpower010 study.

Notably, the benefit with atezolizumab versus best supportive care was greatest in patients with expression of programmed death–ligand 1 (PD-L1) on their tumor, in whom the DFS improvement was a significant 34%.

This is the “first global phase 3 trial using an immune checkpoint inhibitor to show a disease-free survival outcome in early-stage NSCLC,” said lead researcher Heather Wakelee, MD, professor of medicine and chief of the division of oncology at Stanford (Calif.) University Medical Center.

She was speaking at a press briefing ahead of the American Society of Clinical Oncology annual meeting, where the results will be presented on June 6.

Dr. Wakelee added that the “planned analysis for disease-free survival and overall survival in the intention-to-treat populations will continue with longer-term follow-up.”

Asked whether the drug could be recommended for these patients based on the current results, Dr. Wakelee said that “obviously we need approval” for this use from the Food and Drug Administration, but she added that “the FDA has approved other agents, particularly most recently osimertinib [Tagrisso], based on a disease-free survival endpoint.”

These new results show that the benefit with atezolizumab plus chemotherapy is “more profound” than with chemotherapy plus best supportive care, “and therefore, to me, it would be something I would want to offer my patients in that setting.”

Dr. Wakelee also emphasized the importance of screening for lung cancer, so that the disease is detected at earlier stages “when it is potentially curable.”

She also stressed the importance of biomarker testing for patients with resected disease “to look for EGFR mutations, which can be treated with EGFR [tyrosine kinase inhibitors] and also, at some point, to check for PD-L1 ... because, in this trial, the vast majority of benefit” appeared to be in those with PD-L1 expression on their tumors.

Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, said that “immune checkpoint inhibitors have certainly changed the treatment landscape for many types of cancers” and the current study “is the first time we’ve seen an immunotherapy that’s effective in treating early-stage NSCLC.”

“This is an important advance in understanding the role of immunotherapy in earlier stage lung cancer” and “potentially a step forward for many patients.”
 

Study details 

The standard of care for many stage IB-IIIA NSCLC patients “has not changed for many years,” despite “significant progress” having been made in the treatment of more advanced disease, Dr. Wakelee commented.

Consequently, the majority of patients with resected NSCLC continue to receive adjuvant platinum-based chemotherapy, which has been shown to reduce the risk of disease recurrence by 16% in those with completely resected disease.

The new study set out to examine the benefit of adding atezolizumab to adjuvant chemotherapy in the global phase 3 IMpower010 study.

Patients had to have stage IB-IIIA NSCLC, with stage IB tumors at least 4 cm in size, and tumor tissue available for PD-L1 analysis. Following complete resection, 1,280 patients were given up to four cycles of adjuvant platinum-based chemotherapy.

Of those, 1,005 patients were then randomly assigned 1:1 to receive either 16 cycles of atezolizumab 1,200 mg IV every 3 weeks or best supportive care.

The interim results show that, after a median follow-up of 32.8 months, the addition of atezolizumab significantly reduced the risk of recurrence or death versus best supportive care in patients whose tumors had PD-L1 expression of at least 1%, at a hazard ratio of 0.66 (P = .004).

At 24 months, the DFS rate was 74.6% among patients given atezolizumab versus 61% in those receiving best supportive care, reducing to 60% and 48.2%, respectively, at 36 months.

When looking across all randomized patients, the addition of atezolizumab was associated with a smaller reduction in the risk of recurrence of death versus best supportive care, at a hazard ratio of 0.79 after a median follow-up of 32.2 months (P = .02).

On the intention to treat analysis, the reduction in the risk of recurrence or death with atezolizumab was of borderline significance, at a hazard ratio of 0.81 after a median follow-up of 32.2 months (P = .04).

Dr. Wakelee pointed out that patients with stage IB disease, who represented around 12% of those in the trial, “tend to do better and we require longer time to see some of the disease recurrence outcomes,” and so these results are “preliminary.”

She also emphasized that the overall survival data are not yet mature and survival was not formally tested in the current analysis.

In terms of safety, the adverse event profile with atezolizumab was consistent with previous reports, the investigators noted in the abstract. However, Dr. Wakelee said at the briefing that “we had to stop treatment with atezolizumab in 18% of patients because of toxicity.”

All-grade adverse events were reported in 70.7% of the best supportive care group versus 92.7% among those given atezolizumab, while grade 3-4 adverse events were reported in 11.5% and 21.8% of patients, respectively.

The study was funded by Hoffmann–La Roche. Dr. Wakelee reported relationships with AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Helsinn Therapeutics, Janssen Oncology, Mirati Therapeutics, Xcovery, ACEA Biosciences, Arrys Therapeutics, AstraZeneca/MedImmune, Bristol-Myers Squibb, Celgene, Clovis Oncology, Exelixis, Genentech/Roche, Gilead Sciences, Merck, Novartis, Pharmacyclics, Seattle Genetics, and Xcovery. She also reports uncompensated relationships with Genentech/Roche, Merck, and Takeda. Dr. Gralow reported relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Immunotherapy has already had a huge impact on treatment of patients with later stages of non–small cell lung cancer (NSCLC): new clinical data are now showing benefits in patients with earlier stage disease.

Patients with stage IB-IIIA NSCLC showed a markedly improved disease-free survival (DFS) when atezolizumab (Tecentriq) was added onto adjuvant chemotherapy following resection, according to results from an interim analysis of the IMpower010 study.

Notably, the benefit with atezolizumab versus best supportive care was greatest in patients with expression of programmed death–ligand 1 (PD-L1) on their tumor, in whom the DFS improvement was a significant 34%.

This is the “first global phase 3 trial using an immune checkpoint inhibitor to show a disease-free survival outcome in early-stage NSCLC,” said lead researcher Heather Wakelee, MD, professor of medicine and chief of the division of oncology at Stanford (Calif.) University Medical Center.

She was speaking at a press briefing ahead of the American Society of Clinical Oncology annual meeting, where the results will be presented on June 6.

Dr. Wakelee added that the “planned analysis for disease-free survival and overall survival in the intention-to-treat populations will continue with longer-term follow-up.”

Asked whether the drug could be recommended for these patients based on the current results, Dr. Wakelee said that “obviously we need approval” for this use from the Food and Drug Administration, but she added that “the FDA has approved other agents, particularly most recently osimertinib [Tagrisso], based on a disease-free survival endpoint.”

These new results show that the benefit with atezolizumab plus chemotherapy is “more profound” than with chemotherapy plus best supportive care, “and therefore, to me, it would be something I would want to offer my patients in that setting.”

Dr. Wakelee also emphasized the importance of screening for lung cancer, so that the disease is detected at earlier stages “when it is potentially curable.”

She also stressed the importance of biomarker testing for patients with resected disease “to look for EGFR mutations, which can be treated with EGFR [tyrosine kinase inhibitors] and also, at some point, to check for PD-L1 ... because, in this trial, the vast majority of benefit” appeared to be in those with PD-L1 expression on their tumors.

Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, said that “immune checkpoint inhibitors have certainly changed the treatment landscape for many types of cancers” and the current study “is the first time we’ve seen an immunotherapy that’s effective in treating early-stage NSCLC.”

“This is an important advance in understanding the role of immunotherapy in earlier stage lung cancer” and “potentially a step forward for many patients.”
 

Study details 

The standard of care for many stage IB-IIIA NSCLC patients “has not changed for many years,” despite “significant progress” having been made in the treatment of more advanced disease, Dr. Wakelee commented.

Consequently, the majority of patients with resected NSCLC continue to receive adjuvant platinum-based chemotherapy, which has been shown to reduce the risk of disease recurrence by 16% in those with completely resected disease.

The new study set out to examine the benefit of adding atezolizumab to adjuvant chemotherapy in the global phase 3 IMpower010 study.

Patients had to have stage IB-IIIA NSCLC, with stage IB tumors at least 4 cm in size, and tumor tissue available for PD-L1 analysis. Following complete resection, 1,280 patients were given up to four cycles of adjuvant platinum-based chemotherapy.

Of those, 1,005 patients were then randomly assigned 1:1 to receive either 16 cycles of atezolizumab 1,200 mg IV every 3 weeks or best supportive care.

The interim results show that, after a median follow-up of 32.8 months, the addition of atezolizumab significantly reduced the risk of recurrence or death versus best supportive care in patients whose tumors had PD-L1 expression of at least 1%, at a hazard ratio of 0.66 (P = .004).

At 24 months, the DFS rate was 74.6% among patients given atezolizumab versus 61% in those receiving best supportive care, reducing to 60% and 48.2%, respectively, at 36 months.

When looking across all randomized patients, the addition of atezolizumab was associated with a smaller reduction in the risk of recurrence of death versus best supportive care, at a hazard ratio of 0.79 after a median follow-up of 32.2 months (P = .02).

On the intention to treat analysis, the reduction in the risk of recurrence or death with atezolizumab was of borderline significance, at a hazard ratio of 0.81 after a median follow-up of 32.2 months (P = .04).

Dr. Wakelee pointed out that patients with stage IB disease, who represented around 12% of those in the trial, “tend to do better and we require longer time to see some of the disease recurrence outcomes,” and so these results are “preliminary.”

She also emphasized that the overall survival data are not yet mature and survival was not formally tested in the current analysis.

In terms of safety, the adverse event profile with atezolizumab was consistent with previous reports, the investigators noted in the abstract. However, Dr. Wakelee said at the briefing that “we had to stop treatment with atezolizumab in 18% of patients because of toxicity.”

All-grade adverse events were reported in 70.7% of the best supportive care group versus 92.7% among those given atezolizumab, while grade 3-4 adverse events were reported in 11.5% and 21.8% of patients, respectively.

The study was funded by Hoffmann–La Roche. Dr. Wakelee reported relationships with AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Helsinn Therapeutics, Janssen Oncology, Mirati Therapeutics, Xcovery, ACEA Biosciences, Arrys Therapeutics, AstraZeneca/MedImmune, Bristol-Myers Squibb, Celgene, Clovis Oncology, Exelixis, Genentech/Roche, Gilead Sciences, Merck, Novartis, Pharmacyclics, Seattle Genetics, and Xcovery. She also reports uncompensated relationships with Genentech/Roche, Merck, and Takeda. Dr. Gralow reported relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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