Lung Cancer

Patients with COVID-19 and progressing cancer had a fivefold increase in the risk of 30-day mortality, compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer, according to data from the COVID-19 and Cancer Consortium (CCC19) registry.

Mongkolchon Akesin/Shutterstock

Other independent risk factors for death in patients with COVID-19 and cancer were older age, male sex, former smoking, number of comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater, and treatment with hydroxychloroquine plus azithromycin.

In fact, patients who received hydroxychloroquine and azithromycin had a nearly threefold higher risk of death than did patients who had not received the combination. However, this finding was of “uncertain validity due to a high risk of residual confounding; for example, patients receiving this combination were more likely to have severe disease or more likely to be hospitalized,” said Jeremy L. Warner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee.

Dr. Warner presented these findings in an online press briefing. Additional findings from the CCC19 registry are set to be presented as part of the American Society of Clinical Oncology (ASCO) virtual scientific program. The findings were also published in The Lancet.

‘Severe impact’ in cancer patients

“For people with cancer, the impact of COVID-19 is especially severe, whether they have been exposed to the virus or not. Patients with cancer are typically older adults, often with other underlying conditions, and their immune systems may be suppressed by the cancer, or due to chemotherapy, radiation, or other treatment,” commented ASCO President Howard A. Burris III, MD, who moderated the press briefing but was not involved in the study of CCC19 registry data.

“ASCO members tell us that they have had to delay or modify treatment plans to reduce patients’ risk of infection, and we’re unclear what the impact of these changes will be. Delays in cancer screening and diagnosis are also a major concern,” Dr. Burris continued.

“This does confirm reports that have come out from other centers, including other parts of the world, where they have found that people who have cancer and COVID-19 have a worse outcome,” said Andrew T. Chan, MD, MPH, of Massachusetts General Hospital in Boston, who was not involved in the research.

Dr. Chan’s group has developed a COVID-19 symptom study app with the aim of defining whether people living with cancer are at increased risk for infections, in addition to whether cancer is an independent risk factor for COVID-19 severity or mortality.

“Using data from our app, we were able to show that people who reported living with cancer did have a higher risk of developing COVID and were more likely to be hospitalized related to COVID,” Dr. Chan said in an interview.
 

Study details

The CCC19 registry collects information from 104 participating institutions in the United States and Canada, as well as anonymous data from individuals in the United States, Argentina, Canada, the European Union, and the United Kingdom.

The sample of 928 patients Dr. Warner presented was evenly balanced by sex. The median age was 66 years, and 30% of patients were aged 75 years or older.

In all, 39% of patients were on active anticancer therapy, and 43% had measurable disease. Breast cancer was the most common diagnosis, followed by prostate cancer, gastrointestinal cancers, lymphomas, and thoracic cancers.

Two-thirds of the patients (68%) had an ECOG performance status of 0 or 1, 8% had a performance status of 2, and 5% a status of 3 or 4. The remaining patients had unknown performance status.

Slightly more than half of patients (52%) were never smokers, 37% were former smokers, and 5% were current smokers. The remaining 6% of patients had unknown smoking status.

At a median follow-up of 21 days, 121 patients (13%) had died. All deaths occurred within 30 days of COVID-19 diagnosis. Among patients who died, 78 were male, 64 were former smokers, 70 were aged 75 years or older, 41 had active stable or responding cancer, 25 had progressing cancer, and 42 had an ECOG performance status of 2 or higher.

In all, 466 patients were hospitalized, and 106 in this group (23%) died. Among the 132 patients admitted to an ICU, 50 (38%) died, including 27 patients aged 75 years or older, and 15 with an ECOG performance status of 2 or greater. Of the 116 patients who required intubation, 50 (43%) died, including 26 who were 75 years or older, and 11 who had a performance status of 2 or greater.

It’s early days yet, and a larger sample size with longer follow-up will be needed to get a more complete picture of how COVID-19 affects specific patient subsets over time, Dr. Warner said.

ASCO has established its own COVID-19 registry to collect both near-term and longitudinal data during the pandemic.

“We’ll be able to learn about both how the pandemic has impacted delivery of cancer care, as well as the longer-term effects of COVID-19 on cancer patients and understand what care approaches are working best,” said Richard L. Schilsky, MD, chief medical officer and executive vice president of ASCO, during the briefing.

The study of CCC19 registry data was supported in part by the National Institutes of Health and the American Cancer Society. Dr. Warner disclosed stock/ownership in HemOnc.org, consulting for IBM and Westat, and travel expenses from IBM. Dr. Burris, Dr. Schilsky, and Dr. Chan reported no disclosures relevant to the study.
 

SOURCE: Warner J L et al. ASCO 2020, Abstract LBA110.

Patients with COVID-19 and progressing cancer had a fivefold increase in the risk of 30-day mortality, compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer, according to data from the COVID-19 and Cancer Consortium (CCC19) registry.

Mongkolchon Akesin/Shutterstock

Other independent risk factors for death in patients with COVID-19 and cancer were older age, male sex, former smoking, number of comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater, and treatment with hydroxychloroquine plus azithromycin.

In fact, patients who received hydroxychloroquine and azithromycin had a nearly threefold higher risk of death than did patients who had not received the combination. However, this finding was of “uncertain validity due to a high risk of residual confounding; for example, patients receiving this combination were more likely to have severe disease or more likely to be hospitalized,” said Jeremy L. Warner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee.

Dr. Warner presented these findings in an online press briefing. Additional findings from the CCC19 registry are set to be presented as part of the American Society of Clinical Oncology (ASCO) virtual scientific program. The findings were also published in The Lancet.

‘Severe impact’ in cancer patients

“For people with cancer, the impact of COVID-19 is especially severe, whether they have been exposed to the virus or not. Patients with cancer are typically older adults, often with other underlying conditions, and their immune systems may be suppressed by the cancer, or due to chemotherapy, radiation, or other treatment,” commented ASCO President Howard A. Burris III, MD, who moderated the press briefing but was not involved in the study of CCC19 registry data.

“ASCO members tell us that they have had to delay or modify treatment plans to reduce patients’ risk of infection, and we’re unclear what the impact of these changes will be. Delays in cancer screening and diagnosis are also a major concern,” Dr. Burris continued.

“This does confirm reports that have come out from other centers, including other parts of the world, where they have found that people who have cancer and COVID-19 have a worse outcome,” said Andrew T. Chan, MD, MPH, of Massachusetts General Hospital in Boston, who was not involved in the research.

Dr. Chan’s group has developed a COVID-19 symptom study app with the aim of defining whether people living with cancer are at increased risk for infections, in addition to whether cancer is an independent risk factor for COVID-19 severity or mortality.

“Using data from our app, we were able to show that people who reported living with cancer did have a higher risk of developing COVID and were more likely to be hospitalized related to COVID,” Dr. Chan said in an interview.
 

Study details

The CCC19 registry collects information from 104 participating institutions in the United States and Canada, as well as anonymous data from individuals in the United States, Argentina, Canada, the European Union, and the United Kingdom.

The sample of 928 patients Dr. Warner presented was evenly balanced by sex. The median age was 66 years, and 30% of patients were aged 75 years or older.

In all, 39% of patients were on active anticancer therapy, and 43% had measurable disease. Breast cancer was the most common diagnosis, followed by prostate cancer, gastrointestinal cancers, lymphomas, and thoracic cancers.

Two-thirds of the patients (68%) had an ECOG performance status of 0 or 1, 8% had a performance status of 2, and 5% a status of 3 or 4. The remaining patients had unknown performance status.

Slightly more than half of patients (52%) were never smokers, 37% were former smokers, and 5% were current smokers. The remaining 6% of patients had unknown smoking status.

At a median follow-up of 21 days, 121 patients (13%) had died. All deaths occurred within 30 days of COVID-19 diagnosis. Among patients who died, 78 were male, 64 were former smokers, 70 were aged 75 years or older, 41 had active stable or responding cancer, 25 had progressing cancer, and 42 had an ECOG performance status of 2 or higher.

In all, 466 patients were hospitalized, and 106 in this group (23%) died. Among the 132 patients admitted to an ICU, 50 (38%) died, including 27 patients aged 75 years or older, and 15 with an ECOG performance status of 2 or greater. Of the 116 patients who required intubation, 50 (43%) died, including 26 who were 75 years or older, and 11 who had a performance status of 2 or greater.

It’s early days yet, and a larger sample size with longer follow-up will be needed to get a more complete picture of how COVID-19 affects specific patient subsets over time, Dr. Warner said.

ASCO has established its own COVID-19 registry to collect both near-term and longitudinal data during the pandemic.

“We’ll be able to learn about both how the pandemic has impacted delivery of cancer care, as well as the longer-term effects of COVID-19 on cancer patients and understand what care approaches are working best,” said Richard L. Schilsky, MD, chief medical officer and executive vice president of ASCO, during the briefing.

The study of CCC19 registry data was supported in part by the National Institutes of Health and the American Cancer Society. Dr. Warner disclosed stock/ownership in HemOnc.org, consulting for IBM and Westat, and travel expenses from IBM. Dr. Burris, Dr. Schilsky, and Dr. Chan reported no disclosures relevant to the study.
 

SOURCE: Warner J L et al. ASCO 2020, Abstract LBA110.

Patients with COVID-19 and progressing cancer had a fivefold increase in the risk of 30-day mortality, compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer, according to data from the COVID-19 and Cancer Consortium (CCC19) registry.

Mongkolchon Akesin/Shutterstock

Other independent risk factors for death in patients with COVID-19 and cancer were older age, male sex, former smoking, number of comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater, and treatment with hydroxychloroquine plus azithromycin.

In fact, patients who received hydroxychloroquine and azithromycin had a nearly threefold higher risk of death than did patients who had not received the combination. However, this finding was of “uncertain validity due to a high risk of residual confounding; for example, patients receiving this combination were more likely to have severe disease or more likely to be hospitalized,” said Jeremy L. Warner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee.

Dr. Warner presented these findings in an online press briefing. Additional findings from the CCC19 registry are set to be presented as part of the American Society of Clinical Oncology (ASCO) virtual scientific program. The findings were also published in The Lancet.

‘Severe impact’ in cancer patients

“For people with cancer, the impact of COVID-19 is especially severe, whether they have been exposed to the virus or not. Patients with cancer are typically older adults, often with other underlying conditions, and their immune systems may be suppressed by the cancer, or due to chemotherapy, radiation, or other treatment,” commented ASCO President Howard A. Burris III, MD, who moderated the press briefing but was not involved in the study of CCC19 registry data.

“ASCO members tell us that they have had to delay or modify treatment plans to reduce patients’ risk of infection, and we’re unclear what the impact of these changes will be. Delays in cancer screening and diagnosis are also a major concern,” Dr. Burris continued.

“This does confirm reports that have come out from other centers, including other parts of the world, where they have found that people who have cancer and COVID-19 have a worse outcome,” said Andrew T. Chan, MD, MPH, of Massachusetts General Hospital in Boston, who was not involved in the research.

Dr. Chan’s group has developed a COVID-19 symptom study app with the aim of defining whether people living with cancer are at increased risk for infections, in addition to whether cancer is an independent risk factor for COVID-19 severity or mortality.

“Using data from our app, we were able to show that people who reported living with cancer did have a higher risk of developing COVID and were more likely to be hospitalized related to COVID,” Dr. Chan said in an interview.
 

Study details

The CCC19 registry collects information from 104 participating institutions in the United States and Canada, as well as anonymous data from individuals in the United States, Argentina, Canada, the European Union, and the United Kingdom.

The sample of 928 patients Dr. Warner presented was evenly balanced by sex. The median age was 66 years, and 30% of patients were aged 75 years or older.

In all, 39% of patients were on active anticancer therapy, and 43% had measurable disease. Breast cancer was the most common diagnosis, followed by prostate cancer, gastrointestinal cancers, lymphomas, and thoracic cancers.

Two-thirds of the patients (68%) had an ECOG performance status of 0 or 1, 8% had a performance status of 2, and 5% a status of 3 or 4. The remaining patients had unknown performance status.

Slightly more than half of patients (52%) were never smokers, 37% were former smokers, and 5% were current smokers. The remaining 6% of patients had unknown smoking status.

At a median follow-up of 21 days, 121 patients (13%) had died. All deaths occurred within 30 days of COVID-19 diagnosis. Among patients who died, 78 were male, 64 were former smokers, 70 were aged 75 years or older, 41 had active stable or responding cancer, 25 had progressing cancer, and 42 had an ECOG performance status of 2 or higher.

In all, 466 patients were hospitalized, and 106 in this group (23%) died. Among the 132 patients admitted to an ICU, 50 (38%) died, including 27 patients aged 75 years or older, and 15 with an ECOG performance status of 2 or greater. Of the 116 patients who required intubation, 50 (43%) died, including 26 who were 75 years or older, and 11 who had a performance status of 2 or greater.

It’s early days yet, and a larger sample size with longer follow-up will be needed to get a more complete picture of how COVID-19 affects specific patient subsets over time, Dr. Warner said.

ASCO has established its own COVID-19 registry to collect both near-term and longitudinal data during the pandemic.

“We’ll be able to learn about both how the pandemic has impacted delivery of cancer care, as well as the longer-term effects of COVID-19 on cancer patients and understand what care approaches are working best,” said Richard L. Schilsky, MD, chief medical officer and executive vice president of ASCO, during the briefing.

The study of CCC19 registry data was supported in part by the National Institutes of Health and the American Cancer Society. Dr. Warner disclosed stock/ownership in HemOnc.org, consulting for IBM and Westat, and travel expenses from IBM. Dr. Burris, Dr. Schilsky, and Dr. Chan reported no disclosures relevant to the study.
 

SOURCE: Warner J L et al. ASCO 2020, Abstract LBA110.

Adjuvant therapy with osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death in patients with stage IB-IIIA non–small cell lung cancer (NSCLC) bearing EGFR mutations, results of the ADAURA trial showed.

The randomized, phase 3 trial was a comparison of osimertinib treatment with placebo following complete resection of localized or locally advanced NSCLC with negative margins. The trial was unblinded early and halted on the recommendation of the independent data-monitoring committee, due to the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” said study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center and Smilow Cancer Center at Yale University in New Haven, Conn.

Dr. Herbst is scheduled to present results from ADAURA as part of the American Society of Clinical Oncology virtual scientific program.

In an online briefing prior to the meeting, Dr. Herbst said the impressive results reminded him of a lesson imparted by his mentor, the late Isaiah Fidler, DVM, PhD.

“He taught me, he taught all of us, that metastasis is a spread of tumor that kills patients,” Dr. Herbst said. “Drugs such as this, based on biology, given to patients at the earliest possible time, prevent those metastases and allow patients to live longer and with a better quality of life.”

Results from the ADAURA trial provide compelling evidence of the benefit of adjuvant osimertinib for a select group of patients, according to Tina Cascone, MD, PhD, assistant professor in the department of thoracic head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston. She was not involved in the study.

“These are unprecedented results for a potentially curable, resected population of patients,” Dr. Cascone said in an interview. “This definitely has the potential to shift the paradigm in the treatments that we have available for patients with resected disease. It’s very important to emphasize how much we’ve learned from the metastatic setting and how we’re bringing what we’ve learned into early stage disease.”

 

High recurrence rates

An estimated 30% of patients with NSCLC present with resectable disease at diagnosis, but 5-year recurrence rates following surgery and cisplatin-based adjuvant chemotherapy remain high, ranging from 45% among patients with stage IB disease to 62% for patients with stage II NSCLC and 76% for patients with stage III disease, Dr. Herbst noted.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) targeted to EGFR. It has been shown to offer improvements in both progression-free survival and overall survival compared with the EGFR-TKIs erlotinib and gefitinib for patients with advanced EGFR-mutated NSCLC, as well as in patients with central nervous system metastases.

Osimertinib’s efficacy and safety profile against advanced disease suggests it may also be effective against early stage disease, a hypothesis the ADAURA trial was designed to test.
 

Study details

The phase 3, randomized, double-blind trial was conducted at centers in the United States, Europe, Asia, and Australia. A total of 682 patients with completely resected stage IB, II, or IIIA NSCLC, with or without planned adjuvant chemotherapy, were enrolled.

After stratification by stage, EGFR mutation, and race (Asian vs. non-Asian), patients were randomized on a 1:1 basis to receive either osimertinib at 80 mg once daily or placebo. The planned treatment duration was a maximum of 3 years.

Members of the independent data-monitoring committee held a meeting in April 2020. Although they had not planned an efficacy analysis at that time, they decided the results were clearly in favor of osimertinib. So they recommended unblinding and halting of the trial.

At the time of unblinding, the study had completed enrollment, and all patients had been followed for at least 1 year.
 

Efficacy and safety

For the primary endpoint of disease-free survival (DFS) in patients with stage II to IIIA disease, the median DFS was not reached for patients assigned to osimertinib, but it was 20.4 months for patients assigned to placebo (hazard ratio, 0.17; P < .0001).

The numbers were similar for the secondary endpoint of DFS in the overall population, including patients with stage IB disease. The median DFS was not reached for patients on osimertinib but was 28.1 months for patients on placebo (HR, 0.21; P < .0001).

DFS was significantly superior with osimertinib across all subgroups in the overall population, including sex, age, smoking status, race, stage, EGFR mutation, and adjuvant chemotherapy (yes or no).

Dr. Herbst said patients tolerated osimertinib well, and the drug’s safety profile was consistent with that already known. There were no adverse events leading to death in the osimertinib arm, and the incidence of grade 3 or 4 adverse events of any kind was low.

In all, 10 patients (3%) in the osimertinib arm were reported to have interstitial lung disease. Prolongation of the QT interval was reported in 22 patients (7%) on osimertinib and 4 patients (1%) in the placebo arm.

The results show that “adjuvant osimertinib provides a highly effective, practice-changing treatment for patients with stage IB, II, IIIA, EGFR mutation-positive non–small cell lung cancer after complete tumor resection,” Dr. Herbst said.

Dr. Herbst disclosed relationships with AstraZeneca, which funded the study, as well as Jun Shi Pharmaceuticals and other companies. Dr. Cascone is the international principal investigator of the NeoCOAST trial evaluating durvalumab, an AstraZeneca product.

SOURCE: Herbst RS et al. ASCO 2020, Abstract LBA5.

Adjuvant therapy with osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death in patients with stage IB-IIIA non–small cell lung cancer (NSCLC) bearing EGFR mutations, results of the ADAURA trial showed.

The randomized, phase 3 trial was a comparison of osimertinib treatment with placebo following complete resection of localized or locally advanced NSCLC with negative margins. The trial was unblinded early and halted on the recommendation of the independent data-monitoring committee, due to the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” said study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center and Smilow Cancer Center at Yale University in New Haven, Conn.

Dr. Herbst is scheduled to present results from ADAURA as part of the American Society of Clinical Oncology virtual scientific program.

In an online briefing prior to the meeting, Dr. Herbst said the impressive results reminded him of a lesson imparted by his mentor, the late Isaiah Fidler, DVM, PhD.

“He taught me, he taught all of us, that metastasis is a spread of tumor that kills patients,” Dr. Herbst said. “Drugs such as this, based on biology, given to patients at the earliest possible time, prevent those metastases and allow patients to live longer and with a better quality of life.”

Results from the ADAURA trial provide compelling evidence of the benefit of adjuvant osimertinib for a select group of patients, according to Tina Cascone, MD, PhD, assistant professor in the department of thoracic head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston. She was not involved in the study.

“These are unprecedented results for a potentially curable, resected population of patients,” Dr. Cascone said in an interview. “This definitely has the potential to shift the paradigm in the treatments that we have available for patients with resected disease. It’s very important to emphasize how much we’ve learned from the metastatic setting and how we’re bringing what we’ve learned into early stage disease.”

 

High recurrence rates

An estimated 30% of patients with NSCLC present with resectable disease at diagnosis, but 5-year recurrence rates following surgery and cisplatin-based adjuvant chemotherapy remain high, ranging from 45% among patients with stage IB disease to 62% for patients with stage II NSCLC and 76% for patients with stage III disease, Dr. Herbst noted.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) targeted to EGFR. It has been shown to offer improvements in both progression-free survival and overall survival compared with the EGFR-TKIs erlotinib and gefitinib for patients with advanced EGFR-mutated NSCLC, as well as in patients with central nervous system metastases.

Osimertinib’s efficacy and safety profile against advanced disease suggests it may also be effective against early stage disease, a hypothesis the ADAURA trial was designed to test.
 

Study details

The phase 3, randomized, double-blind trial was conducted at centers in the United States, Europe, Asia, and Australia. A total of 682 patients with completely resected stage IB, II, or IIIA NSCLC, with or without planned adjuvant chemotherapy, were enrolled.

After stratification by stage, EGFR mutation, and race (Asian vs. non-Asian), patients were randomized on a 1:1 basis to receive either osimertinib at 80 mg once daily or placebo. The planned treatment duration was a maximum of 3 years.

Members of the independent data-monitoring committee held a meeting in April 2020. Although they had not planned an efficacy analysis at that time, they decided the results were clearly in favor of osimertinib. So they recommended unblinding and halting of the trial.

At the time of unblinding, the study had completed enrollment, and all patients had been followed for at least 1 year.
 

Efficacy and safety

For the primary endpoint of disease-free survival (DFS) in patients with stage II to IIIA disease, the median DFS was not reached for patients assigned to osimertinib, but it was 20.4 months for patients assigned to placebo (hazard ratio, 0.17; P < .0001).

The numbers were similar for the secondary endpoint of DFS in the overall population, including patients with stage IB disease. The median DFS was not reached for patients on osimertinib but was 28.1 months for patients on placebo (HR, 0.21; P < .0001).

DFS was significantly superior with osimertinib across all subgroups in the overall population, including sex, age, smoking status, race, stage, EGFR mutation, and adjuvant chemotherapy (yes or no).

Dr. Herbst said patients tolerated osimertinib well, and the drug’s safety profile was consistent with that already known. There were no adverse events leading to death in the osimertinib arm, and the incidence of grade 3 or 4 adverse events of any kind was low.

In all, 10 patients (3%) in the osimertinib arm were reported to have interstitial lung disease. Prolongation of the QT interval was reported in 22 patients (7%) on osimertinib and 4 patients (1%) in the placebo arm.

The results show that “adjuvant osimertinib provides a highly effective, practice-changing treatment for patients with stage IB, II, IIIA, EGFR mutation-positive non–small cell lung cancer after complete tumor resection,” Dr. Herbst said.

Dr. Herbst disclosed relationships with AstraZeneca, which funded the study, as well as Jun Shi Pharmaceuticals and other companies. Dr. Cascone is the international principal investigator of the NeoCOAST trial evaluating durvalumab, an AstraZeneca product.

SOURCE: Herbst RS et al. ASCO 2020, Abstract LBA5.

Adjuvant therapy with osimertinib was associated with a nearly 80% reduction in the risk of disease recurrence or death in patients with stage IB-IIIA non–small cell lung cancer (NSCLC) bearing EGFR mutations, results of the ADAURA trial showed.

The randomized, phase 3 trial was a comparison of osimertinib treatment with placebo following complete resection of localized or locally advanced NSCLC with negative margins. The trial was unblinded early and halted on the recommendation of the independent data-monitoring committee, due to the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” said study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center and Smilow Cancer Center at Yale University in New Haven, Conn.

Dr. Herbst is scheduled to present results from ADAURA as part of the American Society of Clinical Oncology virtual scientific program.

In an online briefing prior to the meeting, Dr. Herbst said the impressive results reminded him of a lesson imparted by his mentor, the late Isaiah Fidler, DVM, PhD.

“He taught me, he taught all of us, that metastasis is a spread of tumor that kills patients,” Dr. Herbst said. “Drugs such as this, based on biology, given to patients at the earliest possible time, prevent those metastases and allow patients to live longer and with a better quality of life.”

Results from the ADAURA trial provide compelling evidence of the benefit of adjuvant osimertinib for a select group of patients, according to Tina Cascone, MD, PhD, assistant professor in the department of thoracic head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston. She was not involved in the study.

“These are unprecedented results for a potentially curable, resected population of patients,” Dr. Cascone said in an interview. “This definitely has the potential to shift the paradigm in the treatments that we have available for patients with resected disease. It’s very important to emphasize how much we’ve learned from the metastatic setting and how we’re bringing what we’ve learned into early stage disease.”

 

High recurrence rates

An estimated 30% of patients with NSCLC present with resectable disease at diagnosis, but 5-year recurrence rates following surgery and cisplatin-based adjuvant chemotherapy remain high, ranging from 45% among patients with stage IB disease to 62% for patients with stage II NSCLC and 76% for patients with stage III disease, Dr. Herbst noted.

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) targeted to EGFR. It has been shown to offer improvements in both progression-free survival and overall survival compared with the EGFR-TKIs erlotinib and gefitinib for patients with advanced EGFR-mutated NSCLC, as well as in patients with central nervous system metastases.

Osimertinib’s efficacy and safety profile against advanced disease suggests it may also be effective against early stage disease, a hypothesis the ADAURA trial was designed to test.
 

Study details

The phase 3, randomized, double-blind trial was conducted at centers in the United States, Europe, Asia, and Australia. A total of 682 patients with completely resected stage IB, II, or IIIA NSCLC, with or without planned adjuvant chemotherapy, were enrolled.

After stratification by stage, EGFR mutation, and race (Asian vs. non-Asian), patients were randomized on a 1:1 basis to receive either osimertinib at 80 mg once daily or placebo. The planned treatment duration was a maximum of 3 years.

Members of the independent data-monitoring committee held a meeting in April 2020. Although they had not planned an efficacy analysis at that time, they decided the results were clearly in favor of osimertinib. So they recommended unblinding and halting of the trial.

At the time of unblinding, the study had completed enrollment, and all patients had been followed for at least 1 year.
 

Efficacy and safety

For the primary endpoint of disease-free survival (DFS) in patients with stage II to IIIA disease, the median DFS was not reached for patients assigned to osimertinib, but it was 20.4 months for patients assigned to placebo (hazard ratio, 0.17; P < .0001).

The numbers were similar for the secondary endpoint of DFS in the overall population, including patients with stage IB disease. The median DFS was not reached for patients on osimertinib but was 28.1 months for patients on placebo (HR, 0.21; P < .0001).

DFS was significantly superior with osimertinib across all subgroups in the overall population, including sex, age, smoking status, race, stage, EGFR mutation, and adjuvant chemotherapy (yes or no).

Dr. Herbst said patients tolerated osimertinib well, and the drug’s safety profile was consistent with that already known. There were no adverse events leading to death in the osimertinib arm, and the incidence of grade 3 or 4 adverse events of any kind was low.

In all, 10 patients (3%) in the osimertinib arm were reported to have interstitial lung disease. Prolongation of the QT interval was reported in 22 patients (7%) on osimertinib and 4 patients (1%) in the placebo arm.

The results show that “adjuvant osimertinib provides a highly effective, practice-changing treatment for patients with stage IB, II, IIIA, EGFR mutation-positive non–small cell lung cancer after complete tumor resection,” Dr. Herbst said.

Dr. Herbst disclosed relationships with AstraZeneca, which funded the study, as well as Jun Shi Pharmaceuticals and other companies. Dr. Cascone is the international principal investigator of the NeoCOAST trial evaluating durvalumab, an AstraZeneca product.

SOURCE: Herbst RS et al. ASCO 2020, Abstract LBA5.

The Food and Drug Administration has approved the combination of nivolumab (Opdivo), ipilimumab (Yervoy), and two cycles of platinum-doublet chemotherapy as frontline treatment for patients with metastatic or recurrent non–small cell lung cancer (NSCLC) who have no EGFR or ALK genomic tumor aberrations.

The FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Singapore’s Health Sciences Authority on the review that led to this approval, as part of Project Orbis. The FDA approved the application 2 months ahead of schedule.

The combination chemotherapy was investigated in the CHECKMATE-9LA trial (NCT03215706), which enrolled patients with metastatic or recurrent NSCLC.

Patients were randomized to receive nivolumab plus ipilimumab and two cycles of platinum-doublet chemotherapy (n = 361) or platinum-doublet chemotherapy for four cycles (n = 358).

There was a significant overall survival benefit in the nivolumab-ipilimumab arm, compared with the chemotherapy-only arm. The median overall survival was 14.1 months and 10.7 months, respectively (hazard ratio, 0.69; P = .0006).

The median progression-free survival was 6.8 months in the nivolumab-ipilimumab arm and 5 months in the chemotherapy-only arm (HR, 0.70; P = .0001). The overall response rate was 38% and 25%, respectively (P = .0003).

The most common adverse events in the nivolumab-ipilimumab arm, which occurred in at least 20% of patients, were fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.

Serious adverse events occurred in 57% of patients in the nivolumab-ipilimumab arm. Fatal adverse events occurred in seven patients (2%) in that arm. Fatal events were hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia.

For more details, see the full prescribing information for nivolumab or ipilimumab. Nivolumab and ipilimumab are both products of Bristol-Myers Squibb.

The Food and Drug Administration has approved the combination of nivolumab (Opdivo), ipilimumab (Yervoy), and two cycles of platinum-doublet chemotherapy as frontline treatment for patients with metastatic or recurrent non–small cell lung cancer (NSCLC) who have no EGFR or ALK genomic tumor aberrations.

The FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Singapore’s Health Sciences Authority on the review that led to this approval, as part of Project Orbis. The FDA approved the application 2 months ahead of schedule.

The combination chemotherapy was investigated in the CHECKMATE-9LA trial (NCT03215706), which enrolled patients with metastatic or recurrent NSCLC.

Patients were randomized to receive nivolumab plus ipilimumab and two cycles of platinum-doublet chemotherapy (n = 361) or platinum-doublet chemotherapy for four cycles (n = 358).

There was a significant overall survival benefit in the nivolumab-ipilimumab arm, compared with the chemotherapy-only arm. The median overall survival was 14.1 months and 10.7 months, respectively (hazard ratio, 0.69; P = .0006).

The median progression-free survival was 6.8 months in the nivolumab-ipilimumab arm and 5 months in the chemotherapy-only arm (HR, 0.70; P = .0001). The overall response rate was 38% and 25%, respectively (P = .0003).

The most common adverse events in the nivolumab-ipilimumab arm, which occurred in at least 20% of patients, were fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.

Serious adverse events occurred in 57% of patients in the nivolumab-ipilimumab arm. Fatal adverse events occurred in seven patients (2%) in that arm. Fatal events were hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia.

For more details, see the full prescribing information for nivolumab or ipilimumab. Nivolumab and ipilimumab are both products of Bristol-Myers Squibb.

The Food and Drug Administration has approved the combination of nivolumab (Opdivo), ipilimumab (Yervoy), and two cycles of platinum-doublet chemotherapy as frontline treatment for patients with metastatic or recurrent non–small cell lung cancer (NSCLC) who have no EGFR or ALK genomic tumor aberrations.

The FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Singapore’s Health Sciences Authority on the review that led to this approval, as part of Project Orbis. The FDA approved the application 2 months ahead of schedule.

The combination chemotherapy was investigated in the CHECKMATE-9LA trial (NCT03215706), which enrolled patients with metastatic or recurrent NSCLC.

Patients were randomized to receive nivolumab plus ipilimumab and two cycles of platinum-doublet chemotherapy (n = 361) or platinum-doublet chemotherapy for four cycles (n = 358).

There was a significant overall survival benefit in the nivolumab-ipilimumab arm, compared with the chemotherapy-only arm. The median overall survival was 14.1 months and 10.7 months, respectively (hazard ratio, 0.69; P = .0006).

The median progression-free survival was 6.8 months in the nivolumab-ipilimumab arm and 5 months in the chemotherapy-only arm (HR, 0.70; P = .0001). The overall response rate was 38% and 25%, respectively (P = .0003).

The most common adverse events in the nivolumab-ipilimumab arm, which occurred in at least 20% of patients, were fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, constipation, and pruritus.

Serious adverse events occurred in 57% of patients in the nivolumab-ipilimumab arm. Fatal adverse events occurred in seven patients (2%) in that arm. Fatal events were hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia.

For more details, see the full prescribing information for nivolumab or ipilimumab. Nivolumab and ipilimumab are both products of Bristol-Myers Squibb.

The Food and Drug Administration has approved brigatinib (Alunbrig) to treat adults with ALK-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Brigatinib and the companion diagnostic were both evaluated in the ALTA 1L trial (NCT02737501). The trial enrolled adults with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients had to have an ALK rearrangement based on a local standard of care test.

Clinical samples from trial participants were retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the 275 patients enrolled in the trial, 239 were ALK positive according to the test. Results were negative for 20 patients and unavailable for 16 patients.

Patients were randomized to receive brigatinib at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib at 250 mg twice daily (n = 138).

The estimated median progression-free survival was 24 months in the brigatinib arm and 11 months in the crizotinib arm (hazard ratio, 0.49; P < .0001). The overall response rate was 74% in the brigatinib arm and 62% in the crizotinib arm.

The most common adverse events in the brigatinib arm, occurring in at least 20% of patients, were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, abdominal pain, pruritus, back pain, and dyspnea.

Serious adverse events occurred in 33% of patients in the brigatinib arm, and fatal adverse events included in 2.9%. The fatal events were pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

For more details on the ALTA 1L trial, see the full prescribing information for brigatinib.

The approval of brigatinib was granted to ARIAD Pharmaceuticals. The approval of the Vysis ALK Break Apart FISH Probe Kit was granted to Abbott Molecular.

The Food and Drug Administration has approved brigatinib (Alunbrig) to treat adults with ALK-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Brigatinib and the companion diagnostic were both evaluated in the ALTA 1L trial (NCT02737501). The trial enrolled adults with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients had to have an ALK rearrangement based on a local standard of care test.

Clinical samples from trial participants were retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the 275 patients enrolled in the trial, 239 were ALK positive according to the test. Results were negative for 20 patients and unavailable for 16 patients.

Patients were randomized to receive brigatinib at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib at 250 mg twice daily (n = 138).

The estimated median progression-free survival was 24 months in the brigatinib arm and 11 months in the crizotinib arm (hazard ratio, 0.49; P < .0001). The overall response rate was 74% in the brigatinib arm and 62% in the crizotinib arm.

The most common adverse events in the brigatinib arm, occurring in at least 20% of patients, were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, abdominal pain, pruritus, back pain, and dyspnea.

Serious adverse events occurred in 33% of patients in the brigatinib arm, and fatal adverse events included in 2.9%. The fatal events were pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

For more details on the ALTA 1L trial, see the full prescribing information for brigatinib.

The approval of brigatinib was granted to ARIAD Pharmaceuticals. The approval of the Vysis ALK Break Apart FISH Probe Kit was granted to Abbott Molecular.

The Food and Drug Administration has approved brigatinib (Alunbrig) to treat adults with ALK-positive metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The FDA also approved the Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for brigatinib.

Brigatinib and the companion diagnostic were both evaluated in the ALTA 1L trial (NCT02737501). The trial enrolled adults with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients had to have an ALK rearrangement based on a local standard of care test.

Clinical samples from trial participants were retrospectively tested with the Vysis ALK Break Apart FISH Probe Kit. Of the 275 patients enrolled in the trial, 239 were ALK positive according to the test. Results were negative for 20 patients and unavailable for 16 patients.

Patients were randomized to receive brigatinib at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib at 250 mg twice daily (n = 138).

The estimated median progression-free survival was 24 months in the brigatinib arm and 11 months in the crizotinib arm (hazard ratio, 0.49; P < .0001). The overall response rate was 74% in the brigatinib arm and 62% in the crizotinib arm.

The most common adverse events in the brigatinib arm, occurring in at least 20% of patients, were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, abdominal pain, pruritus, back pain, and dyspnea.

Serious adverse events occurred in 33% of patients in the brigatinib arm, and fatal adverse events included in 2.9%. The fatal events were pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).

For more details on the ALTA 1L trial, see the full prescribing information for brigatinib.

The approval of brigatinib was granted to ARIAD Pharmaceuticals. The approval of the Vysis ALK Break Apart FISH Probe Kit was granted to Abbott Molecular.

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

mzoler@mdedge.com

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

mzoler@mdedge.com

Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.

That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.

“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.

The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.

COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.

“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”

Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”

Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.

Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.

Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”

In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.

The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.

For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.

The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections (Proc Natl Acad Sci. 2020 Apr 29; doi: 10.1073/pnas.2005615117). Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.

LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.

By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.

“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”

The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.

Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.

mzoler@mdedge.com

Low-dose erlotinib is a valid treatment option for elderly and frail patients with non–small cell lung cancer (NSCLC), according to researchers.

They conducted a phase 2 trial to investigate whether one-third of the maximum tolerated dose of erlotinib could maintain sufficient plasma concentration of the drug while avoiding the adverse effects of higher doses. The results were published in JAMA Oncology.

Erlotinib and other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in elderly patients with EGFR-positive NSCLC, according to study author Shingo Miyamoto, MD, of Japanese Red Cross Medical Center in Tokyo, and colleagues.

“With the increasing number of elderly patients with cancer, many of whom also have significant comorbidities, there is a considerable value in investigating whether EGFR-TKIs are effective for the frail population,” the authors wrote. They also noted that it is “difficult to identify the appropriate dose of molecular-targeted drugs.”

With this in mind, Dr. Miyamoto and colleagues conducted a single-arm, phase 2 trial of low-dose erlotinib in 80 chemotherapy-naive frail or elderly patients with EGFR-positive NSCLC. Frailty was defined by age and the Charlson Comorbidity Index. The patients’ median age was 80 years (range, 49-90 years).

Patients received erlotinib at 50 mg per day, which is one-third of the established maximum tolerated dose, for 4 weeks. Then, they were evaluated with radiologic imaging. Treatment continued until disease progression or unacceptable adverse events. Dosing was modified by treatment response or by adverse events.
 

Results

At last follow-up, 7 of the 80 patients were still receiving low-dose erlotinib. Reasons for discontinuation were disease progression (n = 60), patient request (n = 6), adverse events (n = 4), and death (n = 3).

The overall response rate was 60%, and the disease control rate was 90%. The researchers measured plasma erlotinib concentration in 48 patients and found it did not correlate with response.

The median progression-free survival was 9.3 months, and the median overall survival was 26.2 months.

Ten patients had erlotinib temporarily suspended because of adverse events. Five patients had their dose reduced to 25 mg because of adverse events, including oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia.

Two patients discontinued treatment because of adverse events. One patient had a cutaneous ulcer and bone infection. The other had oral mucositis.

Dr. Miyamoto and colleagues concluded that, “low-dose erlotinib was associated with efficacy and safety in frail patients with EGFR mutation–positive lung cancer. More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
 

Less is more

Sometimes, less can be more, said Mellar P. Davis, MD, an oncologist and section head of the palliative care department at Geisinger Medical System in Danville, Penn., who was not involved in this study.

“Why do patients benefit from small doses? It may be that there are fewer drug interruptions over time and patients are able to stay on schedule,” Dr. Davis said. “It may also be that erlotinib clearance is reduced in the elderly and comorbid patient. The reduced dose may, in fact, be the ‘therapeutic’ dose in this special population.”

Plasma levels were frequently in therapeutic ranges in this study, but patients who had subtherapeutic plasma levels also responded to therapy, Dr. Davis pointed out. The lower dose was shown to maintain sufficient concentrations of the treatment while reducing adverse effects.

However, Dr. Davis noted, this was not a randomized trial. “It is always a risk hedging bets on single-arm trials,” he said. “Randomized trials often prove phase 2 single-arm trials wrong.”

He added that quality-of-life measures are absent from the study. Erlotinib is a palliative drug with side effects, Dr. Davis noted.

“Control of cancer and cancer regression should improve symptoms and quality of life when balanced against treatment toxicity,” he said. “In this study, I would have thought that symptom improvement, performance score, and quality of life would have been the primary outcome or the co-primary outcome with disease control.”

Should a randomized, controlled trial of low-dose erlotinib be conducted in the frail/elderly population? “If one believes trials should be quantitatively based, the answer would be no,” Dr. Davis said. “Responses may be the same, and it would be expensive to prove that low-dose erlotinib is the same as standard doses when comparing survival.”

However, if one is interested in quality of life, particularly in this growing population, a trial that incorporated quality-of-life measures would make more sense, according to Dr. Davis. “For if one can achieve less toxicity and treat more patients and get the same duration of clinical benefit, then less will be more,” he concluded.

Dr. Davis reported having no conflicts of interest. Study authors disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and many other companies. Erlotinib is manufactured for OSI Pharmaceuticals, an affiliate of Astellas Pharma, and distributed by Genentech, a member of the Roche Group.

The study was supported by the Japan Agency for Medical Research and Development.

SOURCE: Miyamoto S et al. JAMA Oncol. 2020 May 14; e201250. doi: 10.1001/jamaoncol.2020.1250.

Low-dose erlotinib is a valid treatment option for elderly and frail patients with non–small cell lung cancer (NSCLC), according to researchers.

They conducted a phase 2 trial to investigate whether one-third of the maximum tolerated dose of erlotinib could maintain sufficient plasma concentration of the drug while avoiding the adverse effects of higher doses. The results were published in JAMA Oncology.

Erlotinib and other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in elderly patients with EGFR-positive NSCLC, according to study author Shingo Miyamoto, MD, of Japanese Red Cross Medical Center in Tokyo, and colleagues.

“With the increasing number of elderly patients with cancer, many of whom also have significant comorbidities, there is a considerable value in investigating whether EGFR-TKIs are effective for the frail population,” the authors wrote. They also noted that it is “difficult to identify the appropriate dose of molecular-targeted drugs.”

With this in mind, Dr. Miyamoto and colleagues conducted a single-arm, phase 2 trial of low-dose erlotinib in 80 chemotherapy-naive frail or elderly patients with EGFR-positive NSCLC. Frailty was defined by age and the Charlson Comorbidity Index. The patients’ median age was 80 years (range, 49-90 years).

Patients received erlotinib at 50 mg per day, which is one-third of the established maximum tolerated dose, for 4 weeks. Then, they were evaluated with radiologic imaging. Treatment continued until disease progression or unacceptable adverse events. Dosing was modified by treatment response or by adverse events.
 

Results

At last follow-up, 7 of the 80 patients were still receiving low-dose erlotinib. Reasons for discontinuation were disease progression (n = 60), patient request (n = 6), adverse events (n = 4), and death (n = 3).

The overall response rate was 60%, and the disease control rate was 90%. The researchers measured plasma erlotinib concentration in 48 patients and found it did not correlate with response.

The median progression-free survival was 9.3 months, and the median overall survival was 26.2 months.

Ten patients had erlotinib temporarily suspended because of adverse events. Five patients had their dose reduced to 25 mg because of adverse events, including oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia.

Two patients discontinued treatment because of adverse events. One patient had a cutaneous ulcer and bone infection. The other had oral mucositis.

Dr. Miyamoto and colleagues concluded that, “low-dose erlotinib was associated with efficacy and safety in frail patients with EGFR mutation–positive lung cancer. More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
 

Less is more

Sometimes, less can be more, said Mellar P. Davis, MD, an oncologist and section head of the palliative care department at Geisinger Medical System in Danville, Penn., who was not involved in this study.

“Why do patients benefit from small doses? It may be that there are fewer drug interruptions over time and patients are able to stay on schedule,” Dr. Davis said. “It may also be that erlotinib clearance is reduced in the elderly and comorbid patient. The reduced dose may, in fact, be the ‘therapeutic’ dose in this special population.”

Plasma levels were frequently in therapeutic ranges in this study, but patients who had subtherapeutic plasma levels also responded to therapy, Dr. Davis pointed out. The lower dose was shown to maintain sufficient concentrations of the treatment while reducing adverse effects.

However, Dr. Davis noted, this was not a randomized trial. “It is always a risk hedging bets on single-arm trials,” he said. “Randomized trials often prove phase 2 single-arm trials wrong.”

He added that quality-of-life measures are absent from the study. Erlotinib is a palliative drug with side effects, Dr. Davis noted.

“Control of cancer and cancer regression should improve symptoms and quality of life when balanced against treatment toxicity,” he said. “In this study, I would have thought that symptom improvement, performance score, and quality of life would have been the primary outcome or the co-primary outcome with disease control.”

Should a randomized, controlled trial of low-dose erlotinib be conducted in the frail/elderly population? “If one believes trials should be quantitatively based, the answer would be no,” Dr. Davis said. “Responses may be the same, and it would be expensive to prove that low-dose erlotinib is the same as standard doses when comparing survival.”

However, if one is interested in quality of life, particularly in this growing population, a trial that incorporated quality-of-life measures would make more sense, according to Dr. Davis. “For if one can achieve less toxicity and treat more patients and get the same duration of clinical benefit, then less will be more,” he concluded.

Dr. Davis reported having no conflicts of interest. Study authors disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and many other companies. Erlotinib is manufactured for OSI Pharmaceuticals, an affiliate of Astellas Pharma, and distributed by Genentech, a member of the Roche Group.

The study was supported by the Japan Agency for Medical Research and Development.

SOURCE: Miyamoto S et al. JAMA Oncol. 2020 May 14; e201250. doi: 10.1001/jamaoncol.2020.1250.

Low-dose erlotinib is a valid treatment option for elderly and frail patients with non–small cell lung cancer (NSCLC), according to researchers.

They conducted a phase 2 trial to investigate whether one-third of the maximum tolerated dose of erlotinib could maintain sufficient plasma concentration of the drug while avoiding the adverse effects of higher doses. The results were published in JAMA Oncology.

Erlotinib and other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in elderly patients with EGFR-positive NSCLC, according to study author Shingo Miyamoto, MD, of Japanese Red Cross Medical Center in Tokyo, and colleagues.

“With the increasing number of elderly patients with cancer, many of whom also have significant comorbidities, there is a considerable value in investigating whether EGFR-TKIs are effective for the frail population,” the authors wrote. They also noted that it is “difficult to identify the appropriate dose of molecular-targeted drugs.”

With this in mind, Dr. Miyamoto and colleagues conducted a single-arm, phase 2 trial of low-dose erlotinib in 80 chemotherapy-naive frail or elderly patients with EGFR-positive NSCLC. Frailty was defined by age and the Charlson Comorbidity Index. The patients’ median age was 80 years (range, 49-90 years).

Patients received erlotinib at 50 mg per day, which is one-third of the established maximum tolerated dose, for 4 weeks. Then, they were evaluated with radiologic imaging. Treatment continued until disease progression or unacceptable adverse events. Dosing was modified by treatment response or by adverse events.
 

Results

At last follow-up, 7 of the 80 patients were still receiving low-dose erlotinib. Reasons for discontinuation were disease progression (n = 60), patient request (n = 6), adverse events (n = 4), and death (n = 3).

The overall response rate was 60%, and the disease control rate was 90%. The researchers measured plasma erlotinib concentration in 48 patients and found it did not correlate with response.

The median progression-free survival was 9.3 months, and the median overall survival was 26.2 months.

Ten patients had erlotinib temporarily suspended because of adverse events. Five patients had their dose reduced to 25 mg because of adverse events, including oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia.

Two patients discontinued treatment because of adverse events. One patient had a cutaneous ulcer and bone infection. The other had oral mucositis.

Dr. Miyamoto and colleagues concluded that, “low-dose erlotinib was associated with efficacy and safety in frail patients with EGFR mutation–positive lung cancer. More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
 

Less is more

Sometimes, less can be more, said Mellar P. Davis, MD, an oncologist and section head of the palliative care department at Geisinger Medical System in Danville, Penn., who was not involved in this study.

“Why do patients benefit from small doses? It may be that there are fewer drug interruptions over time and patients are able to stay on schedule,” Dr. Davis said. “It may also be that erlotinib clearance is reduced in the elderly and comorbid patient. The reduced dose may, in fact, be the ‘therapeutic’ dose in this special population.”

Plasma levels were frequently in therapeutic ranges in this study, but patients who had subtherapeutic plasma levels also responded to therapy, Dr. Davis pointed out. The lower dose was shown to maintain sufficient concentrations of the treatment while reducing adverse effects.

However, Dr. Davis noted, this was not a randomized trial. “It is always a risk hedging bets on single-arm trials,” he said. “Randomized trials often prove phase 2 single-arm trials wrong.”

He added that quality-of-life measures are absent from the study. Erlotinib is a palliative drug with side effects, Dr. Davis noted.

“Control of cancer and cancer regression should improve symptoms and quality of life when balanced against treatment toxicity,” he said. “In this study, I would have thought that symptom improvement, performance score, and quality of life would have been the primary outcome or the co-primary outcome with disease control.”

Should a randomized, controlled trial of low-dose erlotinib be conducted in the frail/elderly population? “If one believes trials should be quantitatively based, the answer would be no,” Dr. Davis said. “Responses may be the same, and it would be expensive to prove that low-dose erlotinib is the same as standard doses when comparing survival.”

However, if one is interested in quality of life, particularly in this growing population, a trial that incorporated quality-of-life measures would make more sense, according to Dr. Davis. “For if one can achieve less toxicity and treat more patients and get the same duration of clinical benefit, then less will be more,” he concluded.

Dr. Davis reported having no conflicts of interest. Study authors disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and many other companies. Erlotinib is manufactured for OSI Pharmaceuticals, an affiliate of Astellas Pharma, and distributed by Genentech, a member of the Roche Group.

The study was supported by the Japan Agency for Medical Research and Development.

SOURCE: Miyamoto S et al. JAMA Oncol. 2020 May 14; e201250. doi: 10.1001/jamaoncol.2020.1250.

Oncologists continue to rank above the middle range for all specialties in annual compensation for physicians, according to findings from the newly released Medscape Oncologist Compensation Report 2020.

The average earnings for oncologists who participated in the survey was $377,000, which was a 5% increase from the $359,000 reported for 2018.

Just over two-thirds (67%) of oncologists reported that they felt that they were fairly compensated, which is quite a jump from 53% last year.

In addition, oncologists appear to be very satisfied with their profession. Similar to last year’s findings, 84% said they would choose medicine again, and 96% said they would choose the specialty of oncology again.
 

Earning in top third of all specialties

The average annual earnings reported by oncologists put this specialty in eleventh place among 29 specialties. Orthopedic specialists remain at the head of the list, with estimated earnings of $511,000, followed by plastic surgeons ($479,000), otolaryngologists ($455,000), and cardiologists ($438,000), according to Medscape’s compensation report, which included responses from 17,461 physicians in over 30 specialties.

At the bottom of the estimated earnings list were public health and preventive medicine doctors and pediatricians. For both specialties, the reported annual earnings was $232,000. Family medicine specialists were only marginally higher at $234,000.

Radiologists ($427,000), gastroenterologists ($419,000), and urologists ($417,000) all reported higher earnings than oncologists, whereas neurologists, at $280,000, rheumatologists, at $262,000, and internal medicine physicians, at $251,000, earned less.

The report also found that gender disparities in income persist, with male oncologists earning 17% more than their female colleagues. The gender gap in oncology is somewhat less than that seen for all specialties combined, in which men earned 31% more than women, similar to last year’s figure of 33%.

Male oncologists reported spending 38.8 hours per week seeing patients, compared with 34.9 hours reported by female oncologists. This could be a factor contributing to the gender pay disparity. Overall, the average amount of time seeing patients was 37.9 hours per week.
 

Frustrations with paperwork and denied claims

Surveyed oncologists cited some of the frustrations they are facing, such as spending nearly 17 hours a week on paperwork and administrative tasks. They reported that 16% of claims are denied or have to be resubmitted. As for the most challenging part of the job, oncologists (22%), similar to physicians overall (26%), found that having so many rules and regulations takes first place, followed by working with electronic health record systems (20%), difficulties getting fair reimbursement (19%), having to work long hours (12%), and dealing with difficult patients (8%). Few oncologists were concerned about lawsuits (4%), and 4% reported that there were no challenges.

Oncologists reported that the most rewarding part of their job was gratitude/relationships with patients (31%), followed by knowing that they are making the world a better place (27%). After that, oncologists agreed with statements about being very good at what they do/finding answers/diagnoses (22%), having pride in being a doctor (9%), and making good money at a job they like (8%).
 

Other key findings

Other key findings from the Medscape Oncologist Compensation Report 2020 included the following:

• Regarding payment models, 80% take insurance, 41% are in fee-for-service arrangements, and 18% are in accountable care organizations (21%). Only 3% are in direct primary care, and 1% are cash-only practices or have a concierge practice.
• 65% of oncologists state that they will continue taking new and current Medicare/Medicaid patients. None said that they would not take on new Medicare/Medicaid patients, and 35% remain undecided. These numbers differed from physicians overall; 73% of all physicians surveyed said they would continue taking new/current Medicare/Medicaid patients, 6% said that will not take on new Medicare patients, and 4% said they will not take new Medicaid patients. In addition, 3% and 2% said that they would stop treating some or all of their Medicare and Medicaid patients, respectively.
• About half (51%) of oncologists use nurse practitioners, about a third (34%) use physician assistants, and 37% use neither. This was about the same as physicians overall.
• A larger percentage of oncologists (38%) expect to participate in MIPS (merit-based incentive payment system), and only 8% expect to participate in APMs (alternative payment models). This was similar to the findings for physicians overall, with more than one-third (37%) expecting to participate in MIPS and 9% planning to take part in APMs.

Impact of COVID-19 pandemic

The Medscape compensation reports also gives a glimpse of the impact the COVID-19 pandemic is having on physician compensation.

Since the beginning of the pandemic, practices have reported a 55% decrease in revenue and a 60% drop in patient volume. Physician practices and hospitals have laid off or furloughed personnel and have cut pay, and 9% of practices have closed their doors, at least for the time being.

A total of 43,000 health care workers were laid off in March, the report notes.

The findings tie in with those reported elsewhere. For example, a survey conducted by the Medical Group Management Association, which was reported by Medscape Medical News, found that 97% of physician practices have experienced negative financial effects directly or indirectly related to COVID-19.

Specialties were hard hit, especially those that rely on elective procedures, such as dermatology and cardiology. Oncology care has also been disrupted. For example, a survey conducted by the American Cancer Society Cancer Action Network found that half of the cancer patients and survivors who responded reported changes, delays, or disruptions to the care they were receiving.

This article first appeared on Medscape.com.

Oncologists continue to rank above the middle range for all specialties in annual compensation for physicians, according to findings from the newly released Medscape Oncologist Compensation Report 2020.

The average earnings for oncologists who participated in the survey was $377,000, which was a 5% increase from the $359,000 reported for 2018.

Just over two-thirds (67%) of oncologists reported that they felt that they were fairly compensated, which is quite a jump from 53% last year.

In addition, oncologists appear to be very satisfied with their profession. Similar to last year’s findings, 84% said they would choose medicine again, and 96% said they would choose the specialty of oncology again.
 

Earning in top third of all specialties

The average annual earnings reported by oncologists put this specialty in eleventh place among 29 specialties. Orthopedic specialists remain at the head of the list, with estimated earnings of $511,000, followed by plastic surgeons ($479,000), otolaryngologists ($455,000), and cardiologists ($438,000), according to Medscape’s compensation report, which included responses from 17,461 physicians in over 30 specialties.

At the bottom of the estimated earnings list were public health and preventive medicine doctors and pediatricians. For both specialties, the reported annual earnings was $232,000. Family medicine specialists were only marginally higher at $234,000.

Radiologists ($427,000), gastroenterologists ($419,000), and urologists ($417,000) all reported higher earnings than oncologists, whereas neurologists, at $280,000, rheumatologists, at $262,000, and internal medicine physicians, at $251,000, earned less.

The report also found that gender disparities in income persist, with male oncologists earning 17% more than their female colleagues. The gender gap in oncology is somewhat less than that seen for all specialties combined, in which men earned 31% more than women, similar to last year’s figure of 33%.

Male oncologists reported spending 38.8 hours per week seeing patients, compared with 34.9 hours reported by female oncologists. This could be a factor contributing to the gender pay disparity. Overall, the average amount of time seeing patients was 37.9 hours per week.
 

Frustrations with paperwork and denied claims

Surveyed oncologists cited some of the frustrations they are facing, such as spending nearly 17 hours a week on paperwork and administrative tasks. They reported that 16% of claims are denied or have to be resubmitted. As for the most challenging part of the job, oncologists (22%), similar to physicians overall (26%), found that having so many rules and regulations takes first place, followed by working with electronic health record systems (20%), difficulties getting fair reimbursement (19%), having to work long hours (12%), and dealing with difficult patients (8%). Few oncologists were concerned about lawsuits (4%), and 4% reported that there were no challenges.

Oncologists reported that the most rewarding part of their job was gratitude/relationships with patients (31%), followed by knowing that they are making the world a better place (27%). After that, oncologists agreed with statements about being very good at what they do/finding answers/diagnoses (22%), having pride in being a doctor (9%), and making good money at a job they like (8%).
 

Other key findings

Other key findings from the Medscape Oncologist Compensation Report 2020 included the following:

• Regarding payment models, 80% take insurance, 41% are in fee-for-service arrangements, and 18% are in accountable care organizations (21%). Only 3% are in direct primary care, and 1% are cash-only practices or have a concierge practice.
• 65% of oncologists state that they will continue taking new and current Medicare/Medicaid patients. None said that they would not take on new Medicare/Medicaid patients, and 35% remain undecided. These numbers differed from physicians overall; 73% of all physicians surveyed said they would continue taking new/current Medicare/Medicaid patients, 6% said that will not take on new Medicare patients, and 4% said they will not take new Medicaid patients. In addition, 3% and 2% said that they would stop treating some or all of their Medicare and Medicaid patients, respectively.
• About half (51%) of oncologists use nurse practitioners, about a third (34%) use physician assistants, and 37% use neither. This was about the same as physicians overall.
• A larger percentage of oncologists (38%) expect to participate in MIPS (merit-based incentive payment system), and only 8% expect to participate in APMs (alternative payment models). This was similar to the findings for physicians overall, with more than one-third (37%) expecting to participate in MIPS and 9% planning to take part in APMs.

Impact of COVID-19 pandemic

The Medscape compensation reports also gives a glimpse of the impact the COVID-19 pandemic is having on physician compensation.

Since the beginning of the pandemic, practices have reported a 55% decrease in revenue and a 60% drop in patient volume. Physician practices and hospitals have laid off or furloughed personnel and have cut pay, and 9% of practices have closed their doors, at least for the time being.

A total of 43,000 health care workers were laid off in March, the report notes.

The findings tie in with those reported elsewhere. For example, a survey conducted by the Medical Group Management Association, which was reported by Medscape Medical News, found that 97% of physician practices have experienced negative financial effects directly or indirectly related to COVID-19.

Specialties were hard hit, especially those that rely on elective procedures, such as dermatology and cardiology. Oncology care has also been disrupted. For example, a survey conducted by the American Cancer Society Cancer Action Network found that half of the cancer patients and survivors who responded reported changes, delays, or disruptions to the care they were receiving.

This article first appeared on Medscape.com.

Oncologists continue to rank above the middle range for all specialties in annual compensation for physicians, according to findings from the newly released Medscape Oncologist Compensation Report 2020.

The average earnings for oncologists who participated in the survey was $377,000, which was a 5% increase from the $359,000 reported for 2018.

Just over two-thirds (67%) of oncologists reported that they felt that they were fairly compensated, which is quite a jump from 53% last year.

In addition, oncologists appear to be very satisfied with their profession. Similar to last year’s findings, 84% said they would choose medicine again, and 96% said they would choose the specialty of oncology again.
 

Earning in top third of all specialties

The average annual earnings reported by oncologists put this specialty in eleventh place among 29 specialties. Orthopedic specialists remain at the head of the list, with estimated earnings of $511,000, followed by plastic surgeons ($479,000), otolaryngologists ($455,000), and cardiologists ($438,000), according to Medscape’s compensation report, which included responses from 17,461 physicians in over 30 specialties.

At the bottom of the estimated earnings list were public health and preventive medicine doctors and pediatricians. For both specialties, the reported annual earnings was $232,000. Family medicine specialists were only marginally higher at $234,000.

Radiologists ($427,000), gastroenterologists ($419,000), and urologists ($417,000) all reported higher earnings than oncologists, whereas neurologists, at $280,000, rheumatologists, at $262,000, and internal medicine physicians, at $251,000, earned less.

The report also found that gender disparities in income persist, with male oncologists earning 17% more than their female colleagues. The gender gap in oncology is somewhat less than that seen for all specialties combined, in which men earned 31% more than women, similar to last year’s figure of 33%.

Male oncologists reported spending 38.8 hours per week seeing patients, compared with 34.9 hours reported by female oncologists. This could be a factor contributing to the gender pay disparity. Overall, the average amount of time seeing patients was 37.9 hours per week.
 

Frustrations with paperwork and denied claims

Surveyed oncologists cited some of the frustrations they are facing, such as spending nearly 17 hours a week on paperwork and administrative tasks. They reported that 16% of claims are denied or have to be resubmitted. As for the most challenging part of the job, oncologists (22%), similar to physicians overall (26%), found that having so many rules and regulations takes first place, followed by working with electronic health record systems (20%), difficulties getting fair reimbursement (19%), having to work long hours (12%), and dealing with difficult patients (8%). Few oncologists were concerned about lawsuits (4%), and 4% reported that there were no challenges.

Oncologists reported that the most rewarding part of their job was gratitude/relationships with patients (31%), followed by knowing that they are making the world a better place (27%). After that, oncologists agreed with statements about being very good at what they do/finding answers/diagnoses (22%), having pride in being a doctor (9%), and making good money at a job they like (8%).
 

Other key findings

Other key findings from the Medscape Oncologist Compensation Report 2020 included the following:

• Regarding payment models, 80% take insurance, 41% are in fee-for-service arrangements, and 18% are in accountable care organizations (21%). Only 3% are in direct primary care, and 1% are cash-only practices or have a concierge practice.
• 65% of oncologists state that they will continue taking new and current Medicare/Medicaid patients. None said that they would not take on new Medicare/Medicaid patients, and 35% remain undecided. These numbers differed from physicians overall; 73% of all physicians surveyed said they would continue taking new/current Medicare/Medicaid patients, 6% said that will not take on new Medicare patients, and 4% said they will not take new Medicaid patients. In addition, 3% and 2% said that they would stop treating some or all of their Medicare and Medicaid patients, respectively.
• About half (51%) of oncologists use nurse practitioners, about a third (34%) use physician assistants, and 37% use neither. This was about the same as physicians overall.
• A larger percentage of oncologists (38%) expect to participate in MIPS (merit-based incentive payment system), and only 8% expect to participate in APMs (alternative payment models). This was similar to the findings for physicians overall, with more than one-third (37%) expecting to participate in MIPS and 9% planning to take part in APMs.

Impact of COVID-19 pandemic

The Medscape compensation reports also gives a glimpse of the impact the COVID-19 pandemic is having on physician compensation.

Since the beginning of the pandemic, practices have reported a 55% decrease in revenue and a 60% drop in patient volume. Physician practices and hospitals have laid off or furloughed personnel and have cut pay, and 9% of practices have closed their doors, at least for the time being.

A total of 43,000 health care workers were laid off in March, the report notes.

The findings tie in with those reported elsewhere. For example, a survey conducted by the Medical Group Management Association, which was reported by Medscape Medical News, found that 97% of physician practices have experienced negative financial effects directly or indirectly related to COVID-19.

Specialties were hard hit, especially those that rely on elective procedures, such as dermatology and cardiology. Oncology care has also been disrupted. For example, a survey conducted by the American Cancer Society Cancer Action Network found that half of the cancer patients and survivors who responded reported changes, delays, or disruptions to the care they were receiving.

This article first appeared on Medscape.com.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

The Food and Drug Administration has expanded the approved indication for atezolizumab (Tecentriq) in patients with non–small cell lung cancer (NSCLC).

Atezolizumab is now approved as first-line monotherapy for adults with metastatic NSCLC whose tumors are EGFR and ALK wild-type but have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells or PD-L1 stained tumor-infiltrating immune cells covering ≥10% of the tumor area).

The FDA also approved the VENTANA PD-L1 (SP142) Assay as a companion diagnostic to identify patients with NSCLC who are eligible for treatment with atezolizumab.

The drug was evaluated in the IMpower110 trial (NCT02409342), which enrolled patients with stage IV, PD-L1–positive (tumor cells [TC] ≥1% or immune cells [IC] ≥1%) NSCLC who had received no prior chemotherapy for metastatic disease.

The patients were randomized to receive atezolizumab at 1,200 mg every 3 weeks (n = 286) or platinum-based chemotherapy (n = 263), which consisted of carboplatin or cisplatin with either pemetrexed or gemcitabine, until disease progression or unacceptable toxicity.

Overall survival was superior in the atezolizumab arm, but only among patients with high PD-L1 expression (TC ≥50% or IC ≥10%). The median overall survival was 20.2 months among PD-L1–high patients in the atezolizumab arm and 13.1 months among PD-L1–high patients in the chemotherapy arm (hazard ratio, 0.59; P = .0106). There was no significant difference in overall survival between the treatment arms for patients in the other two PD-L1 subgroups – TC ≥5% or IC ≥5% and TC ≥1% or IC ≥1%.

Serious adverse events occurred in 28% of patients receiving atezolizumab. The most frequent of these were pneumonia (2.8%), chronic obstructive pulmonary disease (2.1%), and pneumonitis (2.1%). Fatal adverse events in the atezolizumab arm included unexplained death, aspiration, chronic obstructive pulmonary disease, pulmonary embolism, acute myocardial infarction, cardiac arrest, mechanical ileus, sepsis, cerebral infraction, and device occlusion (one patient each).

For more details on atezolizumab, see the full prescribing information.

The FDA has granted the approval of atezolizumab to Genentech and the approval of the VENTANA PD-L1 (SP142) Assay to Ventana Medical Systems.

Virtually all oncologists, at one time or another, have treated a patient who defied the odds and achieved an unexpectedly long-lasting response. These “exceptional responders” are patients who experience a unique response to therapies that have largely failed to be effective for others with similar cancers.

Genetic and molecular mechanisms may partly account for these responses and may offer clues about why the treatment works for only a few and not for others. To delve more deeply into that area of research, the National Cancer Institute (NCI) began the Exceptional Responders Initiative (ERI) with the goal of identifying potential biological processes that may be responsible, at least in part, for these unusual responses.

NCI researchers have now successfully completed a pilot study that analyzed tumor specimens from more than 100 cases, and the study has affirmed the feasibility of this approach.

Of these cases, six were identified as involving potentially clinically actionable germline mutations.

The findings were published online ahead of print in the Journal of the National Cancer Institute.

“Clearly, the analysis and validation of these results will prove critical to determining the success of this approach,” write James M. Ford, MD, and Beverly S. Mitchell, MD, both of Stanford University School of Medicine, California, in an accompanying editorial. “Ultimately, prospective studies of tumors from exceptional responders, particularly to novel, genomically-targeted agents, may provide a powerful approach to cancer treatment discoveries.”
 

A special case

Molecular profiling technology, including next-generation sequencing, has significantly changed the landscape of the development of cancer therapies, and clinical trials in early drug development are increasingly selecting patients on the basis of molecular alterations.

The ERI grew out of several meetings held by the NCI in 2013 and 2014. It was built on the ability to profile archived tumor material, explained study author S. Percy Ivy, PhD, associate chief of the Investigational Drug Branch in the Division of Cancer Treatment and Diagnosis of the NCI. “This made it possible to collect cases from participating clinicians from all over the country.

“Published cases included patients treated with a targeted therapy but not treated with knowledge of their tumor’s genomics, who then later turned out to have genomic changes that made their tumor exquisitely sensitive to inhibition of a driving pathway,” she said. “There have been published cases as well as cases in the experience of practicing oncologists that seem to do much better than expected.

“We wondered if we could find molecular reasons why tumors respond not only to targeted therapies but also to standard chemotherapy,” said Percy. “If so, we could refine our choice of therapy to patients who are most likely to respond to it.”’

On its website, the NCI writes that there was a particular case that triggered the interest in going ahead with this initiative. Mutations in the TSC1 and NF2 genes, which result in a loss of gene function, were detected in a patient with metastatic bladder cancer. In a clinical trial, the patient was treated with everolimus (Afinitor, Novartis), an inhibitor of the mammalian target of rapamycin (mTORC1), and achieved a complete response with a duration of more than 2 years.

In a separate analysis, researchers sequenced tumors from 96 other individuals with high-grade bladder cancer and identified five TSC1 gene mutations. Tumors were sequenced from 13 patients with bladder cancer who had received everolimus. Results showed that 3 of 4 patients with TSC1 gene mutations experienced some degree of tumor shrinkage after treatment; 8 of 9 patients who did not have the mutation experienced disease progression.

The NCI notes that in “subsequent workshops and discussions, it became obvious that all clinicians have seen a few exceptional responders.”
 

Testing for feasibility

The aim of the current study was to assess the feasibility and potential usefulness of sequencing DNA and RNA from clinical tumor specimens from patients who had experienced unusually profound or durable responses to systemic therapy.

Its main feasibility goal was to identify at least 100 cases involving exceptional responders whose cases could be analyzed in less than 3 years.

An exceptional patient was defined as one who had experienced a complete response to one or more drugs in which complete responses were seen in fewer than 10% of patients who received similar treatment; or a partial response lasting at least 6 months in which such a response is seen in fewer than 10% of patients who receive similar treatment; or a complete or partial response of a duration that is three times the median response duration represented in the literature for the treatment.

Studying exceptional responders presents many challenges, the first being to define what an exceptional response is and what it is not, explained Ivy. “This definition relies on the existence of data that a particular therapy will produce particular responses in groups of patients with similar tumors, as defined by organ of origin,” she said.

Other challenges include obtaining tumor tissue and all the relevant clinical data, such as the number of prior treatments and the patient’s response, as well as any known molecular characteristics (eg, HER2/NEU amplification, estrogen-receptor expression, germline mutations). “We also do not have data on other exposures, such as smoking or chemical exposure,” she said. “In addition, when patients are not on clinical trial, the data are not uniformly obtained ― such as that scans may not be performed at particular intervals.”

Importantly, the molecular tools used to analyze tumors were not available in the past, so many trials did not collect tumor tissue for subsequent research. “Even now, we are learning that there are characteristics beyond DNA and RNA that are potentially important to the ability of a tumor to respond, such as the immune system or epigenetic changes,” she said.

From August 2014 to July 2017, a total of 520 cases were proposed by clinicians as possibly involving exceptional responders, and 222 cases met the criteria.

Analyzable tissue was available for 117 patients. Most of the responders (n = 80, 68.4%) had been treated with combination chemotherapy regimens; 34 patients (29.0%) had received one or more antiangiogenesis agents. In addition, six patients had an exceptional response following treatment with immune checkpoint inhibitors. The final analysis included 109 cases.

One exceptional responder was a woman with metastatic squamous lung cancer that was treated with paclitaxel and carboplatin. The patient achieved a 41-month complete response (expected rate, <10%). Another patient with esophageal adenocarcinoma who was treated with docetaxel and cisplatin experienced a partial response that lasted 128 months (reported median response duration, 24 months). After the patient’s tumor recurred, he experienced for the second time a response to concurrent chemoradiation with the same drug regimen.

Overall, potentially clinically relevant germline mutations were identified in six tumors. Pathogenic BRCA1 or BRCA2 mutations were found in two breast cancer patients, one patient with non–small cell lung cancer, and one patient with rectal cancer. A breast cancer patient had a pathogenic BRCA1 germline mutation, and another had a likely germline mutation in CHEK2. A patient with poorly differentiated lung cancer and a history of breast cancer had a PALB2 mutation.
 

Future steps

Molecular mechanisms are important, but other factors could also play a role in eliciting a response. One is the presence of comorbidities, which was not assessed in the study. Ivy noted that comorbidities could be very important to responses, along with medications that the patient is using for different types of ailments. In addition, the use of complementary and alternative medicines may also have an impact.

“As the field matures, we hope that others will collect these and other characteristics, so that all the data could be used to develop hypotheses about molecular and other factors that can better predict response or resistance,” she said.

The results from this pilot study demonstrated feasibility. Ivy noted that “additional collaboration in similar studies would be welcome, as would methods to use data from various sources to improve our ability to correlate patient characteristics, tumor characteristics and response.

“We envision a larger national and international effort to collect more exceptional responder cases, including more from patients treated with targeted therapies,” she added. “The NCI has been meeting with an interest group that focuses on ER cases in the UK, France, Italy, Canada, and Australia, and this collaborative effort is maturing, albeit slowly.”

The project has been funded in whole or in part with federal funds from the NCI and NIH. Ivy has disclosed no relevant financial relationships. Several coauthors report relationships with industry. The editorialists have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Virtually all oncologists, at one time or another, have treated a patient who defied the odds and achieved an unexpectedly long-lasting response. These “exceptional responders” are patients who experience a unique response to therapies that have largely failed to be effective for others with similar cancers.

Genetic and molecular mechanisms may partly account for these responses and may offer clues about why the treatment works for only a few and not for others. To delve more deeply into that area of research, the National Cancer Institute (NCI) began the Exceptional Responders Initiative (ERI) with the goal of identifying potential biological processes that may be responsible, at least in part, for these unusual responses.

NCI researchers have now successfully completed a pilot study that analyzed tumor specimens from more than 100 cases, and the study has affirmed the feasibility of this approach.

Of these cases, six were identified as involving potentially clinically actionable germline mutations.

The findings were published online ahead of print in the Journal of the National Cancer Institute.

“Clearly, the analysis and validation of these results will prove critical to determining the success of this approach,” write James M. Ford, MD, and Beverly S. Mitchell, MD, both of Stanford University School of Medicine, California, in an accompanying editorial. “Ultimately, prospective studies of tumors from exceptional responders, particularly to novel, genomically-targeted agents, may provide a powerful approach to cancer treatment discoveries.”
 

A special case

Molecular profiling technology, including next-generation sequencing, has significantly changed the landscape of the development of cancer therapies, and clinical trials in early drug development are increasingly selecting patients on the basis of molecular alterations.

The ERI grew out of several meetings held by the NCI in 2013 and 2014. It was built on the ability to profile archived tumor material, explained study author S. Percy Ivy, PhD, associate chief of the Investigational Drug Branch in the Division of Cancer Treatment and Diagnosis of the NCI. “This made it possible to collect cases from participating clinicians from all over the country.

“Published cases included patients treated with a targeted therapy but not treated with knowledge of their tumor’s genomics, who then later turned out to have genomic changes that made their tumor exquisitely sensitive to inhibition of a driving pathway,” she said. “There have been published cases as well as cases in the experience of practicing oncologists that seem to do much better than expected.

“We wondered if we could find molecular reasons why tumors respond not only to targeted therapies but also to standard chemotherapy,” said Percy. “If so, we could refine our choice of therapy to patients who are most likely to respond to it.”’

On its website, the NCI writes that there was a particular case that triggered the interest in going ahead with this initiative. Mutations in the TSC1 and NF2 genes, which result in a loss of gene function, were detected in a patient with metastatic bladder cancer. In a clinical trial, the patient was treated with everolimus (Afinitor, Novartis), an inhibitor of the mammalian target of rapamycin (mTORC1), and achieved a complete response with a duration of more than 2 years.

In a separate analysis, researchers sequenced tumors from 96 other individuals with high-grade bladder cancer and identified five TSC1 gene mutations. Tumors were sequenced from 13 patients with bladder cancer who had received everolimus. Results showed that 3 of 4 patients with TSC1 gene mutations experienced some degree of tumor shrinkage after treatment; 8 of 9 patients who did not have the mutation experienced disease progression.

The NCI notes that in “subsequent workshops and discussions, it became obvious that all clinicians have seen a few exceptional responders.”
 

Testing for feasibility

The aim of the current study was to assess the feasibility and potential usefulness of sequencing DNA and RNA from clinical tumor specimens from patients who had experienced unusually profound or durable responses to systemic therapy.

Its main feasibility goal was to identify at least 100 cases involving exceptional responders whose cases could be analyzed in less than 3 years.

An exceptional patient was defined as one who had experienced a complete response to one or more drugs in which complete responses were seen in fewer than 10% of patients who received similar treatment; or a partial response lasting at least 6 months in which such a response is seen in fewer than 10% of patients who receive similar treatment; or a complete or partial response of a duration that is three times the median response duration represented in the literature for the treatment.

Studying exceptional responders presents many challenges, the first being to define what an exceptional response is and what it is not, explained Ivy. “This definition relies on the existence of data that a particular therapy will produce particular responses in groups of patients with similar tumors, as defined by organ of origin,” she said.

Other challenges include obtaining tumor tissue and all the relevant clinical data, such as the number of prior treatments and the patient’s response, as well as any known molecular characteristics (eg, HER2/NEU amplification, estrogen-receptor expression, germline mutations). “We also do not have data on other exposures, such as smoking or chemical exposure,” she said. “In addition, when patients are not on clinical trial, the data are not uniformly obtained ― such as that scans may not be performed at particular intervals.”

Importantly, the molecular tools used to analyze tumors were not available in the past, so many trials did not collect tumor tissue for subsequent research. “Even now, we are learning that there are characteristics beyond DNA and RNA that are potentially important to the ability of a tumor to respond, such as the immune system or epigenetic changes,” she said.

From August 2014 to July 2017, a total of 520 cases were proposed by clinicians as possibly involving exceptional responders, and 222 cases met the criteria.

Analyzable tissue was available for 117 patients. Most of the responders (n = 80, 68.4%) had been treated with combination chemotherapy regimens; 34 patients (29.0%) had received one or more antiangiogenesis agents. In addition, six patients had an exceptional response following treatment with immune checkpoint inhibitors. The final analysis included 109 cases.

One exceptional responder was a woman with metastatic squamous lung cancer that was treated with paclitaxel and carboplatin. The patient achieved a 41-month complete response (expected rate, <10%). Another patient with esophageal adenocarcinoma who was treated with docetaxel and cisplatin experienced a partial response that lasted 128 months (reported median response duration, 24 months). After the patient’s tumor recurred, he experienced for the second time a response to concurrent chemoradiation with the same drug regimen.

Overall, potentially clinically relevant germline mutations were identified in six tumors. Pathogenic BRCA1 or BRCA2 mutations were found in two breast cancer patients, one patient with non–small cell lung cancer, and one patient with rectal cancer. A breast cancer patient had a pathogenic BRCA1 germline mutation, and another had a likely germline mutation in CHEK2. A patient with poorly differentiated lung cancer and a history of breast cancer had a PALB2 mutation.
 

Future steps

Molecular mechanisms are important, but other factors could also play a role in eliciting a response. One is the presence of comorbidities, which was not assessed in the study. Ivy noted that comorbidities could be very important to responses, along with medications that the patient is using for different types of ailments. In addition, the use of complementary and alternative medicines may also have an impact.

“As the field matures, we hope that others will collect these and other characteristics, so that all the data could be used to develop hypotheses about molecular and other factors that can better predict response or resistance,” she said.

The results from this pilot study demonstrated feasibility. Ivy noted that “additional collaboration in similar studies would be welcome, as would methods to use data from various sources to improve our ability to correlate patient characteristics, tumor characteristics and response.

“We envision a larger national and international effort to collect more exceptional responder cases, including more from patients treated with targeted therapies,” she added. “The NCI has been meeting with an interest group that focuses on ER cases in the UK, France, Italy, Canada, and Australia, and this collaborative effort is maturing, albeit slowly.”

The project has been funded in whole or in part with federal funds from the NCI and NIH. Ivy has disclosed no relevant financial relationships. Several coauthors report relationships with industry. The editorialists have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Virtually all oncologists, at one time or another, have treated a patient who defied the odds and achieved an unexpectedly long-lasting response. These “exceptional responders” are patients who experience a unique response to therapies that have largely failed to be effective for others with similar cancers.

Genetic and molecular mechanisms may partly account for these responses and may offer clues about why the treatment works for only a few and not for others. To delve more deeply into that area of research, the National Cancer Institute (NCI) began the Exceptional Responders Initiative (ERI) with the goal of identifying potential biological processes that may be responsible, at least in part, for these unusual responses.

NCI researchers have now successfully completed a pilot study that analyzed tumor specimens from more than 100 cases, and the study has affirmed the feasibility of this approach.

Of these cases, six were identified as involving potentially clinically actionable germline mutations.

The findings were published online ahead of print in the Journal of the National Cancer Institute.

“Clearly, the analysis and validation of these results will prove critical to determining the success of this approach,” write James M. Ford, MD, and Beverly S. Mitchell, MD, both of Stanford University School of Medicine, California, in an accompanying editorial. “Ultimately, prospective studies of tumors from exceptional responders, particularly to novel, genomically-targeted agents, may provide a powerful approach to cancer treatment discoveries.”
 

A special case

Molecular profiling technology, including next-generation sequencing, has significantly changed the landscape of the development of cancer therapies, and clinical trials in early drug development are increasingly selecting patients on the basis of molecular alterations.

The ERI grew out of several meetings held by the NCI in 2013 and 2014. It was built on the ability to profile archived tumor material, explained study author S. Percy Ivy, PhD, associate chief of the Investigational Drug Branch in the Division of Cancer Treatment and Diagnosis of the NCI. “This made it possible to collect cases from participating clinicians from all over the country.

“Published cases included patients treated with a targeted therapy but not treated with knowledge of their tumor’s genomics, who then later turned out to have genomic changes that made their tumor exquisitely sensitive to inhibition of a driving pathway,” she said. “There have been published cases as well as cases in the experience of practicing oncologists that seem to do much better than expected.

“We wondered if we could find molecular reasons why tumors respond not only to targeted therapies but also to standard chemotherapy,” said Percy. “If so, we could refine our choice of therapy to patients who are most likely to respond to it.”’

On its website, the NCI writes that there was a particular case that triggered the interest in going ahead with this initiative. Mutations in the TSC1 and NF2 genes, which result in a loss of gene function, were detected in a patient with metastatic bladder cancer. In a clinical trial, the patient was treated with everolimus (Afinitor, Novartis), an inhibitor of the mammalian target of rapamycin (mTORC1), and achieved a complete response with a duration of more than 2 years.

In a separate analysis, researchers sequenced tumors from 96 other individuals with high-grade bladder cancer and identified five TSC1 gene mutations. Tumors were sequenced from 13 patients with bladder cancer who had received everolimus. Results showed that 3 of 4 patients with TSC1 gene mutations experienced some degree of tumor shrinkage after treatment; 8 of 9 patients who did not have the mutation experienced disease progression.

The NCI notes that in “subsequent workshops and discussions, it became obvious that all clinicians have seen a few exceptional responders.”
 

Testing for feasibility

The aim of the current study was to assess the feasibility and potential usefulness of sequencing DNA and RNA from clinical tumor specimens from patients who had experienced unusually profound or durable responses to systemic therapy.

Its main feasibility goal was to identify at least 100 cases involving exceptional responders whose cases could be analyzed in less than 3 years.

An exceptional patient was defined as one who had experienced a complete response to one or more drugs in which complete responses were seen in fewer than 10% of patients who received similar treatment; or a partial response lasting at least 6 months in which such a response is seen in fewer than 10% of patients who receive similar treatment; or a complete or partial response of a duration that is three times the median response duration represented in the literature for the treatment.

Studying exceptional responders presents many challenges, the first being to define what an exceptional response is and what it is not, explained Ivy. “This definition relies on the existence of data that a particular therapy will produce particular responses in groups of patients with similar tumors, as defined by organ of origin,” she said.

Other challenges include obtaining tumor tissue and all the relevant clinical data, such as the number of prior treatments and the patient’s response, as well as any known molecular characteristics (eg, HER2/NEU amplification, estrogen-receptor expression, germline mutations). “We also do not have data on other exposures, such as smoking or chemical exposure,” she said. “In addition, when patients are not on clinical trial, the data are not uniformly obtained ― such as that scans may not be performed at particular intervals.”

Importantly, the molecular tools used to analyze tumors were not available in the past, so many trials did not collect tumor tissue for subsequent research. “Even now, we are learning that there are characteristics beyond DNA and RNA that are potentially important to the ability of a tumor to respond, such as the immune system or epigenetic changes,” she said.

From August 2014 to July 2017, a total of 520 cases were proposed by clinicians as possibly involving exceptional responders, and 222 cases met the criteria.

Analyzable tissue was available for 117 patients. Most of the responders (n = 80, 68.4%) had been treated with combination chemotherapy regimens; 34 patients (29.0%) had received one or more antiangiogenesis agents. In addition, six patients had an exceptional response following treatment with immune checkpoint inhibitors. The final analysis included 109 cases.

One exceptional responder was a woman with metastatic squamous lung cancer that was treated with paclitaxel and carboplatin. The patient achieved a 41-month complete response (expected rate, <10%). Another patient with esophageal adenocarcinoma who was treated with docetaxel and cisplatin experienced a partial response that lasted 128 months (reported median response duration, 24 months). After the patient’s tumor recurred, he experienced for the second time a response to concurrent chemoradiation with the same drug regimen.

Overall, potentially clinically relevant germline mutations were identified in six tumors. Pathogenic BRCA1 or BRCA2 mutations were found in two breast cancer patients, one patient with non–small cell lung cancer, and one patient with rectal cancer. A breast cancer patient had a pathogenic BRCA1 germline mutation, and another had a likely germline mutation in CHEK2. A patient with poorly differentiated lung cancer and a history of breast cancer had a PALB2 mutation.
 

Future steps

Molecular mechanisms are important, but other factors could also play a role in eliciting a response. One is the presence of comorbidities, which was not assessed in the study. Ivy noted that comorbidities could be very important to responses, along with medications that the patient is using for different types of ailments. In addition, the use of complementary and alternative medicines may also have an impact.

“As the field matures, we hope that others will collect these and other characteristics, so that all the data could be used to develop hypotheses about molecular and other factors that can better predict response or resistance,” she said.

The results from this pilot study demonstrated feasibility. Ivy noted that “additional collaboration in similar studies would be welcome, as would methods to use data from various sources to improve our ability to correlate patient characteristics, tumor characteristics and response.

“We envision a larger national and international effort to collect more exceptional responder cases, including more from patients treated with targeted therapies,” she added. “The NCI has been meeting with an interest group that focuses on ER cases in the UK, France, Italy, Canada, and Australia, and this collaborative effort is maturing, albeit slowly.”

The project has been funded in whole or in part with federal funds from the NCI and NIH. Ivy has disclosed no relevant financial relationships. Several coauthors report relationships with industry. The editorialists have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) today approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%).

Use is limited to patients with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

The FDA also approved a companion diagnostic device, the PD-L1 IHC 28-8 pharmDx (Agilent Technologies), for identifying patients appropriate for the combination treatment.

The approval is based on results from the CHECKMATE-227 study, a randomized, open-label, multipart trial in patients with metastatic or recurrent NSCLC and no prior anticancer therapy.

The findings were first presented at the 2019 European Society of Medical Oncology (ESMO 2019) annual meeting, and simultaneously published online in the New England Journal of Medicine.

In part 1a of the trial, 793 patients were randomly assigned to receive either the combination of nivolumab plus ipilimumab (n = 396) or platinum-doublet chemotherapy (n = 397). Median overall survival was 17.1 months versus 14.9 (hazard ratio, 0.79; 95% confidence interval, 0.67, 0.94; P = .006). Confirmed overall response rate was 36% and 30%.

Median response duration was 23.2 months in the nivolumab-plus-ipilimumab group versus 6.2 months in the platinum-doublet-chemotherapy group.

The most common adverse reactions in 20% or more of patients receiving the combination of nivolumab plus ipilimumab in CHECKMATE-227 were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

At ESMO 2019, study investigator Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, called the results “practice changing.”

But Marina C. Garassino, MD, head of thoracic medical oncology at the National Cancer Institute of Milan, Italy, had a different opinion. She said that although the results “show we have a new treatment option for the first-line treatment of metastatic NSCLC ... we don’t yet know if the findings are practice changing.”

Garassino added that more work is needed to determine which patients are optimally treated with two immunotherapies, with a combination of chemotherapy and immunotherapy, or just with a single agent.

The recommended doses for metastatic NSCLC are nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

More information about the approval is available on the FDA website.

This article first appeared on Medscape.com.