Immuno-oncology

BARCELONA – First-line pembrolizumab provides a durable long-term overall survival (OS) benefit, compared with that of chemotherapy, in patients with advanced nonsquamous non–small cell lung cancer (NSCLC), according to 3-year data from the phase 3 Keynote-024 trial.

As previously reported, first-line treatment with the programmed death-1 (PD-1) inhibitor significantly improved progression-free survival (PFS) and OS, compared with those of platinum-based chemotherapy, and had fewer adverse events after a median of 11.2 months of follow-up in the open-label trial. In 305 patients with advanced NSCLC, high PD-L1 expression, and an absence of targetable epidermal growth factor or anaplastic lymphoma kinase gene alterations, median PFS was 10.3 months vs. 6.0 months, and estimated OS was 80.2% vs. 72.4% in the groups, respectively (hazard ratios, 0.50 and 0.60, respectively).

At 3 years after treatment initiation, median OS was 26.3 months vs. 14.2 months in patients treated with pembrolizumab or chemotherapy (HR, 0.65), respectively, and the OS rates were 43.7% and 24.9%, Martin Reck, MD, reported at the World Conference on Lung Cancer.

This was despite 98 of 151 patients assigned to chemotherapy crossing over to pembrolizumab, Dr. Reck, head of the department of thoracic oncology and the clinical trial department in the department of thoracic oncology at the Lung Clinic Grosshansdorf (Germany), noted at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

Additionally, despite longer mean treatment duration in the pembrolizumab arm than in the chemotherapy arm (11.1 vs. 4.4 months), grade 3-5 treatment-related adverse events were less frequent with pembrolizumab than with chemotherapy (31.2% vs. 53.3%), he said.

Of 38 patients in the pembrolizumab arm who completed 2 years of therapy, 34 were alive at 3 years, and 31 (81.6%) had an objective response, including 2 who had a complete response. Median duration of response was not reached, and OS was 97.4%.

Grade 3-5 adverse events occurred in 5 (13.2%) of those patients; no fatal treatment-related adverse events occurred.

Of note, 7 of 10 patients who completed 2 years of treatment, but who subsequently progressed, experienced an objective response with a second course of pembrolizumab, and 8 remain alive, he said.

Patients in KEYNOTE-024 were randomized to receive 200 mg of pembrolizumab every 3 weeks for 2 years or investigator’s choice of platinum doublet for 4-6 cycles plus optional maintenance, with stratification by performance status, tumor histology, and region.

The findings confirm the long-term efficacy of pembrolizumab, compared with platinum-based chemotherapy, demonstrate “consistent benefit in overall survival ... despite a crossover of 65%,” and show the first signs of efficacy with reexposure to pembrolizumab at the time of progression.

“This is work in progress; currently we have data from 10 [reexposed] patients, but what we do see is clinical activity even after [reexposure] to pembrolizumab, so we do see a stabilization of response to the disease in 70% of the patients, and 50% are ongoing.”

The findings highlight a new reality: “There are really some patients who have this disease as a chronic disease induced by immunotherapy.” Dr. Reck said.

KEYNOTE-024 was funded by Merck Sharp & Dohme. Dr. Reck reported receiving personal fees/honoraria for consultancy and lectures from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Merck Sharp & Dohme, MSD, Eli Lilly, Pfizer, AbbVie, Roche, and Novartis.

SOURCE: Reck M et al. WCLC 2019, Abstract OA14.01.

BARCELONA – First-line pembrolizumab provides a durable long-term overall survival (OS) benefit, compared with that of chemotherapy, in patients with advanced nonsquamous non–small cell lung cancer (NSCLC), according to 3-year data from the phase 3 Keynote-024 trial.

As previously reported, first-line treatment with the programmed death-1 (PD-1) inhibitor significantly improved progression-free survival (PFS) and OS, compared with those of platinum-based chemotherapy, and had fewer adverse events after a median of 11.2 months of follow-up in the open-label trial. In 305 patients with advanced NSCLC, high PD-L1 expression, and an absence of targetable epidermal growth factor or anaplastic lymphoma kinase gene alterations, median PFS was 10.3 months vs. 6.0 months, and estimated OS was 80.2% vs. 72.4% in the groups, respectively (hazard ratios, 0.50 and 0.60, respectively).

At 3 years after treatment initiation, median OS was 26.3 months vs. 14.2 months in patients treated with pembrolizumab or chemotherapy (HR, 0.65), respectively, and the OS rates were 43.7% and 24.9%, Martin Reck, MD, reported at the World Conference on Lung Cancer.

This was despite 98 of 151 patients assigned to chemotherapy crossing over to pembrolizumab, Dr. Reck, head of the department of thoracic oncology and the clinical trial department in the department of thoracic oncology at the Lung Clinic Grosshansdorf (Germany), noted at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

Additionally, despite longer mean treatment duration in the pembrolizumab arm than in the chemotherapy arm (11.1 vs. 4.4 months), grade 3-5 treatment-related adverse events were less frequent with pembrolizumab than with chemotherapy (31.2% vs. 53.3%), he said.

Of 38 patients in the pembrolizumab arm who completed 2 years of therapy, 34 were alive at 3 years, and 31 (81.6%) had an objective response, including 2 who had a complete response. Median duration of response was not reached, and OS was 97.4%.

Grade 3-5 adverse events occurred in 5 (13.2%) of those patients; no fatal treatment-related adverse events occurred.

Of note, 7 of 10 patients who completed 2 years of treatment, but who subsequently progressed, experienced an objective response with a second course of pembrolizumab, and 8 remain alive, he said.

Patients in KEYNOTE-024 were randomized to receive 200 mg of pembrolizumab every 3 weeks for 2 years or investigator’s choice of platinum doublet for 4-6 cycles plus optional maintenance, with stratification by performance status, tumor histology, and region.

The findings confirm the long-term efficacy of pembrolizumab, compared with platinum-based chemotherapy, demonstrate “consistent benefit in overall survival ... despite a crossover of 65%,” and show the first signs of efficacy with reexposure to pembrolizumab at the time of progression.

“This is work in progress; currently we have data from 10 [reexposed] patients, but what we do see is clinical activity even after [reexposure] to pembrolizumab, so we do see a stabilization of response to the disease in 70% of the patients, and 50% are ongoing.”

The findings highlight a new reality: “There are really some patients who have this disease as a chronic disease induced by immunotherapy.” Dr. Reck said.

KEYNOTE-024 was funded by Merck Sharp & Dohme. Dr. Reck reported receiving personal fees/honoraria for consultancy and lectures from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Merck Sharp & Dohme, MSD, Eli Lilly, Pfizer, AbbVie, Roche, and Novartis.

SOURCE: Reck M et al. WCLC 2019, Abstract OA14.01.

BARCELONA – First-line pembrolizumab provides a durable long-term overall survival (OS) benefit, compared with that of chemotherapy, in patients with advanced nonsquamous non–small cell lung cancer (NSCLC), according to 3-year data from the phase 3 Keynote-024 trial.

As previously reported, first-line treatment with the programmed death-1 (PD-1) inhibitor significantly improved progression-free survival (PFS) and OS, compared with those of platinum-based chemotherapy, and had fewer adverse events after a median of 11.2 months of follow-up in the open-label trial. In 305 patients with advanced NSCLC, high PD-L1 expression, and an absence of targetable epidermal growth factor or anaplastic lymphoma kinase gene alterations, median PFS was 10.3 months vs. 6.0 months, and estimated OS was 80.2% vs. 72.4% in the groups, respectively (hazard ratios, 0.50 and 0.60, respectively).

At 3 years after treatment initiation, median OS was 26.3 months vs. 14.2 months in patients treated with pembrolizumab or chemotherapy (HR, 0.65), respectively, and the OS rates were 43.7% and 24.9%, Martin Reck, MD, reported at the World Conference on Lung Cancer.

This was despite 98 of 151 patients assigned to chemotherapy crossing over to pembrolizumab, Dr. Reck, head of the department of thoracic oncology and the clinical trial department in the department of thoracic oncology at the Lung Clinic Grosshansdorf (Germany), noted at the conference, which was sponsored by the International Association for the Study of Lung Cancer.

Additionally, despite longer mean treatment duration in the pembrolizumab arm than in the chemotherapy arm (11.1 vs. 4.4 months), grade 3-5 treatment-related adverse events were less frequent with pembrolizumab than with chemotherapy (31.2% vs. 53.3%), he said.

Of 38 patients in the pembrolizumab arm who completed 2 years of therapy, 34 were alive at 3 years, and 31 (81.6%) had an objective response, including 2 who had a complete response. Median duration of response was not reached, and OS was 97.4%.

Grade 3-5 adverse events occurred in 5 (13.2%) of those patients; no fatal treatment-related adverse events occurred.

Of note, 7 of 10 patients who completed 2 years of treatment, but who subsequently progressed, experienced an objective response with a second course of pembrolizumab, and 8 remain alive, he said.

Patients in KEYNOTE-024 were randomized to receive 200 mg of pembrolizumab every 3 weeks for 2 years or investigator’s choice of platinum doublet for 4-6 cycles plus optional maintenance, with stratification by performance status, tumor histology, and region.

The findings confirm the long-term efficacy of pembrolizumab, compared with platinum-based chemotherapy, demonstrate “consistent benefit in overall survival ... despite a crossover of 65%,” and show the first signs of efficacy with reexposure to pembrolizumab at the time of progression.

“This is work in progress; currently we have data from 10 [reexposed] patients, but what we do see is clinical activity even after [reexposure] to pembrolizumab, so we do see a stabilization of response to the disease in 70% of the patients, and 50% are ongoing.”

The findings highlight a new reality: “There are really some patients who have this disease as a chronic disease induced by immunotherapy.” Dr. Reck said.

KEYNOTE-024 was funded by Merck Sharp & Dohme. Dr. Reck reported receiving personal fees/honoraria for consultancy and lectures from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Merck Sharp & Dohme, MSD, Eli Lilly, Pfizer, AbbVie, Roche, and Novartis.

SOURCE: Reck M et al. WCLC 2019, Abstract OA14.01.

BOSTON – CT103A, a chimeric antigen receptor (CAR) T-cell therapy, is “active and effective” in patients with relapsed/refractory multiple myeloma, according to a speaker at the International Myeloma Workshop, held by the International Myeloma Society.

Jennifer Smith/MDedge News

The anti–B-cell maturation antigen (BCMA) CAR T-cell therapy produced a 100% response rate in patients with heavily pretreated multiple myeloma, and three of four patients who had failed a prior CAR T-cell therapy achieved a stringent complete response after CT103A.

Chunrui Li, MD, PhD, of Tongji Hospital and Tongji Medical College, Huazhong University of Science, Wuhan, China, presented these results at the workshop.

Dr. Li noted that anti-BCMA CAR T-cell therapy has produced responses in myeloma patients, but approximately half of patients typically relapse in about a year. CAR T-cell infusions after relapse have not been effective in these patients.

In an effort to change that, Dr. Li and his colleagues developed CT103A, a lentiviral vector containing a CAR structure with a fully human single-chain fragment variant; CD8a hinger; and transmembrane, 4-1BB co-stimulatory, and CD3z activation domains.

Dr. Li and his colleagues evaluated CT103A in a phase 0 trial (ChiCTR1800018137) of 18 patients who had received at least three prior lines of therapy and had disease refractory to a proteasome inhibitor and an immunomodulatory agent.

The patients’ median age was 53.3 years (range, 38-66 years), and their median time since diagnosis was 32 months (range, 8-92 months). They had received a median of 4 (range, 3-6) prior therapies. All had received prior bortezomib and lenalidomide, seven had undergone a transplant, and four had been treated on a trial of murine anti-BCMA CAR T-cell therapy.

For the current trial, patients received lymphodepletion with cyclophosphamide and fludarabine, followed by CT103A at 1x10⁶, 3x10⁶, or 6x10⁶ CAR T cells/kg.

There was one dose-limiting toxicity at the highest dose level – grade 4 cytokine release syndrome (CRS) in a patient who died at day 19 after CT103A infusion.

In all, 17 patients developed CRS, four with grade 1, eight with grade 2, four with grade 3, and one with grade 4 CRS. None of the patients developed neurologic toxicity.

Serious adverse events related to lymphodepletion and/or CT103A included prolonged cytopenia (n = 3), pulmonary infection (n = 2), herpes zoster (n = 1), pleuritis (n = 1), and hypoxemia (n = 1).

There were 17 patients evaluable for efficacy, and all of them achieved a response at some point. In eight patients, responses have lasted more than 200 days.

At the data cutoff, there were 10 stringent complete responses, two complete responses, and three very good partial responses. One patient progressed after achieving a very good partial response, and one patient achieved a partial response but ultimately died (likely of respiratory failure attributable to a lung infection).

Of the four patients who had previously received murine CAR T-cell therapy, one progressed, and three achieved a stringent complete response.

This study was funded by Nanjing Iaso Biotherapeutics. Dr. Li did not disclose any conflicts of interest.

[email protected]

SOURCE: Li C et al. IMW 2019, Abstract OAB-033.

BOSTON – CT103A, a chimeric antigen receptor (CAR) T-cell therapy, is “active and effective” in patients with relapsed/refractory multiple myeloma, according to a speaker at the International Myeloma Workshop, held by the International Myeloma Society.

Jennifer Smith/MDedge News

The anti–B-cell maturation antigen (BCMA) CAR T-cell therapy produced a 100% response rate in patients with heavily pretreated multiple myeloma, and three of four patients who had failed a prior CAR T-cell therapy achieved a stringent complete response after CT103A.

Chunrui Li, MD, PhD, of Tongji Hospital and Tongji Medical College, Huazhong University of Science, Wuhan, China, presented these results at the workshop.

Dr. Li noted that anti-BCMA CAR T-cell therapy has produced responses in myeloma patients, but approximately half of patients typically relapse in about a year. CAR T-cell infusions after relapse have not been effective in these patients.

In an effort to change that, Dr. Li and his colleagues developed CT103A, a lentiviral vector containing a CAR structure with a fully human single-chain fragment variant; CD8a hinger; and transmembrane, 4-1BB co-stimulatory, and CD3z activation domains.

Dr. Li and his colleagues evaluated CT103A in a phase 0 trial (ChiCTR1800018137) of 18 patients who had received at least three prior lines of therapy and had disease refractory to a proteasome inhibitor and an immunomodulatory agent.

The patients’ median age was 53.3 years (range, 38-66 years), and their median time since diagnosis was 32 months (range, 8-92 months). They had received a median of 4 (range, 3-6) prior therapies. All had received prior bortezomib and lenalidomide, seven had undergone a transplant, and four had been treated on a trial of murine anti-BCMA CAR T-cell therapy.

For the current trial, patients received lymphodepletion with cyclophosphamide and fludarabine, followed by CT103A at 1x10⁶, 3x10⁶, or 6x10⁶ CAR T cells/kg.

There was one dose-limiting toxicity at the highest dose level – grade 4 cytokine release syndrome (CRS) in a patient who died at day 19 after CT103A infusion.

In all, 17 patients developed CRS, four with grade 1, eight with grade 2, four with grade 3, and one with grade 4 CRS. None of the patients developed neurologic toxicity.

Serious adverse events related to lymphodepletion and/or CT103A included prolonged cytopenia (n = 3), pulmonary infection (n = 2), herpes zoster (n = 1), pleuritis (n = 1), and hypoxemia (n = 1).

There were 17 patients evaluable for efficacy, and all of them achieved a response at some point. In eight patients, responses have lasted more than 200 days.

At the data cutoff, there were 10 stringent complete responses, two complete responses, and three very good partial responses. One patient progressed after achieving a very good partial response, and one patient achieved a partial response but ultimately died (likely of respiratory failure attributable to a lung infection).

Of the four patients who had previously received murine CAR T-cell therapy, one progressed, and three achieved a stringent complete response.

This study was funded by Nanjing Iaso Biotherapeutics. Dr. Li did not disclose any conflicts of interest.

[email protected]

SOURCE: Li C et al. IMW 2019, Abstract OAB-033.

BOSTON – CT103A, a chimeric antigen receptor (CAR) T-cell therapy, is “active and effective” in patients with relapsed/refractory multiple myeloma, according to a speaker at the International Myeloma Workshop, held by the International Myeloma Society.

Jennifer Smith/MDedge News

The anti–B-cell maturation antigen (BCMA) CAR T-cell therapy produced a 100% response rate in patients with heavily pretreated multiple myeloma, and three of four patients who had failed a prior CAR T-cell therapy achieved a stringent complete response after CT103A.

Chunrui Li, MD, PhD, of Tongji Hospital and Tongji Medical College, Huazhong University of Science, Wuhan, China, presented these results at the workshop.

Dr. Li noted that anti-BCMA CAR T-cell therapy has produced responses in myeloma patients, but approximately half of patients typically relapse in about a year. CAR T-cell infusions after relapse have not been effective in these patients.

In an effort to change that, Dr. Li and his colleagues developed CT103A, a lentiviral vector containing a CAR structure with a fully human single-chain fragment variant; CD8a hinger; and transmembrane, 4-1BB co-stimulatory, and CD3z activation domains.

Dr. Li and his colleagues evaluated CT103A in a phase 0 trial (ChiCTR1800018137) of 18 patients who had received at least three prior lines of therapy and had disease refractory to a proteasome inhibitor and an immunomodulatory agent.

The patients’ median age was 53.3 years (range, 38-66 years), and their median time since diagnosis was 32 months (range, 8-92 months). They had received a median of 4 (range, 3-6) prior therapies. All had received prior bortezomib and lenalidomide, seven had undergone a transplant, and four had been treated on a trial of murine anti-BCMA CAR T-cell therapy.

For the current trial, patients received lymphodepletion with cyclophosphamide and fludarabine, followed by CT103A at 1x10⁶, 3x10⁶, or 6x10⁶ CAR T cells/kg.

There was one dose-limiting toxicity at the highest dose level – grade 4 cytokine release syndrome (CRS) in a patient who died at day 19 after CT103A infusion.

In all, 17 patients developed CRS, four with grade 1, eight with grade 2, four with grade 3, and one with grade 4 CRS. None of the patients developed neurologic toxicity.

Serious adverse events related to lymphodepletion and/or CT103A included prolonged cytopenia (n = 3), pulmonary infection (n = 2), herpes zoster (n = 1), pleuritis (n = 1), and hypoxemia (n = 1).

There were 17 patients evaluable for efficacy, and all of them achieved a response at some point. In eight patients, responses have lasted more than 200 days.

At the data cutoff, there were 10 stringent complete responses, two complete responses, and three very good partial responses. One patient progressed after achieving a very good partial response, and one patient achieved a partial response but ultimately died (likely of respiratory failure attributable to a lung infection).

Of the four patients who had previously received murine CAR T-cell therapy, one progressed, and three achieved a stringent complete response.

This study was funded by Nanjing Iaso Biotherapeutics. Dr. Li did not disclose any conflicts of interest.

[email protected]

SOURCE: Li C et al. IMW 2019, Abstract OAB-033.

As immunotherapy has become more widely available, cancer patients have been referred to subacute rehabilitation (SAR) facilities at an increasing rate, to become well enough to tolerate treatment, investigators report.

However, “many patients never receive additional therapy and are readmitted or deceased within a short time, marking this population as one with strong needs for concurrent palliative and usual oncology care,” wrote Jonathan C. Yeh, MD, of Johns Hopkins University, Baltimore, and coauthors. Their report is in Journal of Oncology Practice.

To determine if the advent of immunotherapy contributed to an increase in referrals to SAR facilities – and which patients survived long enough to benefit – the researchers reviewed the electronic charts of 358 patients who were referred to such facilities. The number of referrals increased gradually over the 8-year period of the study.

Of these 358 patients, 174 (49%) were seen again in the oncology clinic before readmission or death and 117 (33%) ever received additional cancer-directed treatment. The patients most likely to receive additional treatment were those with leukemia, lymphoma, or localized solid disease.

Of the 413 total discharges, 116 (28%) resulted in hospital readmission within 30 days of discharge. Seventy-four (21%) of the patients were deceased within 30 days; 212 (59%) were deceased within 180 days. Only 123 (30%) of the initial admissions involved a palliative care specialist; this involvement was associated with increases in documented goals of care, completion of advance directives, and election of do-not-resuscitate status.

The authors noted their study’s limitations, including all of the data coming from a single tertiary cancer center. In addition, the data are observational, which made the researchers “unable to control for key patient characteristics such as performance status, patient goals, insurance coverage of trials, and the like.”

Dr. Smith reported being employed by UpToDate and receiving royalties as coeditor of the Oxford Textbook of Cancer Communication. No other conflicts of interest were reported.

SOURCE: Yeh JC et al. J Oncol Pract. 2019 Aug 29. doi: 10.1200/JOP.19.00044.

As immunotherapy has become more widely available, cancer patients have been referred to subacute rehabilitation (SAR) facilities at an increasing rate, to become well enough to tolerate treatment, investigators report.

However, “many patients never receive additional therapy and are readmitted or deceased within a short time, marking this population as one with strong needs for concurrent palliative and usual oncology care,” wrote Jonathan C. Yeh, MD, of Johns Hopkins University, Baltimore, and coauthors. Their report is in Journal of Oncology Practice.

To determine if the advent of immunotherapy contributed to an increase in referrals to SAR facilities – and which patients survived long enough to benefit – the researchers reviewed the electronic charts of 358 patients who were referred to such facilities. The number of referrals increased gradually over the 8-year period of the study.

Of these 358 patients, 174 (49%) were seen again in the oncology clinic before readmission or death and 117 (33%) ever received additional cancer-directed treatment. The patients most likely to receive additional treatment were those with leukemia, lymphoma, or localized solid disease.

Of the 413 total discharges, 116 (28%) resulted in hospital readmission within 30 days of discharge. Seventy-four (21%) of the patients were deceased within 30 days; 212 (59%) were deceased within 180 days. Only 123 (30%) of the initial admissions involved a palliative care specialist; this involvement was associated with increases in documented goals of care, completion of advance directives, and election of do-not-resuscitate status.

The authors noted their study’s limitations, including all of the data coming from a single tertiary cancer center. In addition, the data are observational, which made the researchers “unable to control for key patient characteristics such as performance status, patient goals, insurance coverage of trials, and the like.”

Dr. Smith reported being employed by UpToDate and receiving royalties as coeditor of the Oxford Textbook of Cancer Communication. No other conflicts of interest were reported.

SOURCE: Yeh JC et al. J Oncol Pract. 2019 Aug 29. doi: 10.1200/JOP.19.00044.

As immunotherapy has become more widely available, cancer patients have been referred to subacute rehabilitation (SAR) facilities at an increasing rate, to become well enough to tolerate treatment, investigators report.

However, “many patients never receive additional therapy and are readmitted or deceased within a short time, marking this population as one with strong needs for concurrent palliative and usual oncology care,” wrote Jonathan C. Yeh, MD, of Johns Hopkins University, Baltimore, and coauthors. Their report is in Journal of Oncology Practice.

To determine if the advent of immunotherapy contributed to an increase in referrals to SAR facilities – and which patients survived long enough to benefit – the researchers reviewed the electronic charts of 358 patients who were referred to such facilities. The number of referrals increased gradually over the 8-year period of the study.

Of these 358 patients, 174 (49%) were seen again in the oncology clinic before readmission or death and 117 (33%) ever received additional cancer-directed treatment. The patients most likely to receive additional treatment were those with leukemia, lymphoma, or localized solid disease.

Of the 413 total discharges, 116 (28%) resulted in hospital readmission within 30 days of discharge. Seventy-four (21%) of the patients were deceased within 30 days; 212 (59%) were deceased within 180 days. Only 123 (30%) of the initial admissions involved a palliative care specialist; this involvement was associated with increases in documented goals of care, completion of advance directives, and election of do-not-resuscitate status.

The authors noted their study’s limitations, including all of the data coming from a single tertiary cancer center. In addition, the data are observational, which made the researchers “unable to control for key patient characteristics such as performance status, patient goals, insurance coverage of trials, and the like.”

Dr. Smith reported being employed by UpToDate and receiving royalties as coeditor of the Oxford Textbook of Cancer Communication. No other conflicts of interest were reported.

SOURCE: Yeh JC et al. J Oncol Pract. 2019 Aug 29. doi: 10.1200/JOP.19.00044.

Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.

In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.

A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.

The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.

However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.

The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.

They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.

The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.

“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.

Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.

“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.

The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.

SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.

Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.

In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.

A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.

The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.

However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.

The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.

They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.

The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.

“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.

Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.

“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.

The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.

SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.

Prior antibiotic use may be associated with a reduced treatment response to checkpoint inhibitors, and worse outcomes, in patients with cancer, according to investigators.

In a prospective cohort study, researchers followed 196 patients with cancer who were treated with immune checkpoint inhibitors in routine clinical practice.

A total of 22 patients had been treated with a 7-day or less course of broad-spectrum beta-lactam–based antibiotics in the 30 days prior to starting immune checkpoint inhibitor therapy, and 68 patients were concurrently taking broad-spectrum beta-lactam–based antibiotics with their checkpoint inhibitor therapy.

The analysis revealed that prior antibiotic therapy was associated with nearly a 100% greater likelihood of poor response to checkpoint inhibitor therapy (P less than .001) and significantly worse overall survival (2 vs. 26 months). Patients who had been on prior antibiotic therapy were also more likely to stop checkpoint inhibitor therapy because their disease had progressed, and were more likely to die of progressive disease while on checkpoint inhibitors.

However, concurrent antibiotic use did not appear to affect either treatment response to checkpoint inhibitors or overall survival.

The most common indication for both prior and concurrent antibiotic use was respiratory tract infections. Researchers examined whether cancer type might play a role in contributing to the association; for example, chronic airway disease in lung cancer might mean higher likelihood of antibiotic use but also lower treatment response and survival.

They found that the association between prior antibiotic therapy and overall survival was consistent across the 119 patients with non–small cell lung cancer, the 38 patients with melanoma, and the 39 patients with other tumor types.

The association was also independent of the class of antibiotic used, the patient’s performance status, and their corticosteroid use.

“Broad-spectrum ATB [antibiotic] use can cause prolonged disruption of the gut ecosystem and impair the effectiveness of the cytotoxic T-cell response against cancer, strengthening the biologic plausibility underlying the adverse effect of ATB therapy on immunotherapy outcomes,” wrote Dr. David J. Pinato, from Imperial College London, and coauthors in JAMA Oncology.

Addressing the question of whether comorbidities might be the mediating factor, the authors pointed out that the use of antibiotics during checkpoint inhibitor therapy – which was a potential indicator of patients’ status worsening during treatment – was not associated with reduced response to treatment or lower overall survival.

“Although provision of cATB [concurrent antibiotic] therapy appears to be safe in the context of immunotherapy, clinicians should carefully weigh the pros and cons of prescribing broad-spectrum ATBs prior to ICI [immune checkpoint inhibitor] treatment,” they wrote.

The study was supported by the Imperial College National Institute for Health Research Biomedical Research Centre, the Imperial College Tissue Bank, the Imperial Cancer Research U.K. Centre, the National Institute for Health Research, and the Wellcome Trust Strategic Fund. Two authors reported receiving grant funding and personal fees from the pharmaceutical sector unrelated to the study.

SOURCE: Pinato D et al. JAMA Oncol. 2019 Sep 12. doi: 10.1001/jamaoncol.2019.2785.

Nivolumab has “limited intracranial activity” in patients with clear cell renal cell carcinoma (ccRCC) and previously untreated brain metastases, according to researchers.

In a phase 2 trial, nivolumab produced an intracranial response rate of 12% in ccRCC patients with previously untreated brain metastases.

The median intracranial progression-free survival (PFS) was longer among patients who had received prior focal therapy than among those with previously untreated brain metastases.

These results suggest “brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC,” Ronan Flippot, MD, of Université Paris-Saclay in Villejuif, France, and colleagues wrote in the Journal of Clinical Oncology.

Dr. Flippot and colleagues conducted this analysis of patients from the phase 2 GETUG-AFU 26 NIVOREN trial (NCT03013335). The researchers looked at 73 ccRCC patients with asymptomatic brain metastases who had received at least one prior line of antiangiogenic treatment.

Patients were divided into two cohorts. Cohort A included patients with previously untreated brain metastases (n = 39), and cohort B included patients who had received focal therapy for brain metastases (n = 34).

Baseline characteristics were similar between the cohorts. The median ages were 61 years in cohort A (range, 39-77) and 58 years in cohort B (range, 33-78). Most patients had grade 3-4 tumors (64% in cohort A and 78% in cohort B), and most had one brain lesion (67% and 59%, respectively). The median sum of the diameters of target lesions was 11 mm in cohort A and 17 mm in cohort B.

All patients received intravenous nivolumab at 3 mg/kg every 2 weeks until they progressed, developed unacceptable toxicity, died, withdrew consent, or the investigator stopped treatment.

The median follow-up was 23.6 months in cohort A and 20.2 months in cohort B. The median duration of treatment was 4.9 months and 4.5 months, respectively. Five patients in cohort A and four in cohort B were still receiving nivolumab at the data cutoff.

Response

The primary endpoint was the intracranial response rate in cohort A, which was 12%. All four responders achieved a complete response. At baseline, all of them had grade 1-2 disease and a single brain lesion smaller than 1 cm.

Thirteen patients (38%) in cohort A had stable intracranial disease as their best response, and 17 (50%) had progressive intracranial disease. The remaining five patients could not be evaluated because they progressed and died before the first evaluation.

The extracranial response rate in cohort A was 21%, and all seven responders had partial responses. Ten patients had stable extracranial disease (30%), and 16 had extracranial progression (49%). The remaining six patients were not evaluable for extracranial response.

All four patients who achieved a complete intracranial response had a partial extracranial response. Six patients (18%) had discordant intracranial and extracranial responses.
 

Survival

The median intracranial PFS in cohort A was 2.7 months in cohort A versus 4.8 months in cohort B. When the researchers adjusted for baseline characteristics, they found that prior focal therapy decreased the risk of intracranial progression (hazard ratio, 0.49).

The median extracranial PFS was 2.8 months in cohort A versus 2.6 months in cohort B. The median global PFS was 2.4 months in cohort A versus 2.5 months in cohort B.

The overall survival rates at 12 months were 66.7% in cohort A and 58.8% in cohort B.

Safety

The most common treatment-related adverse events (in cohort A and B, respectively) were asthenia (21% and 24%) and rash (10% and 9%).

Grade 3/4 treatment-related adverse events occurred in four patients in cohort A and five in cohort B. In cohort A, these events were asthenia, elevated liver function tests, dyspnea, and atrioventricular block. In cohort B, the events were diarrhea, musculoskeletal pain, psoriasis, hypophosphatemia, and elevated creatinine (in two patients).

The patient who developed atrioventricular block permanently discontinued nivolumab. There were no other treatment-related adverse events that led to discontinuation.

This study was supported by Bristol-Myers Squibb. The researchers disclosed relationships with Bristol-Myers Squibb and many other companies.

SOURCE: Flippot R et al. J Clin Oncol. 2019 Aug 10;37(23):2008-16.

Nivolumab has “limited intracranial activity” in patients with clear cell renal cell carcinoma (ccRCC) and previously untreated brain metastases, according to researchers.

In a phase 2 trial, nivolumab produced an intracranial response rate of 12% in ccRCC patients with previously untreated brain metastases.

The median intracranial progression-free survival (PFS) was longer among patients who had received prior focal therapy than among those with previously untreated brain metastases.

These results suggest “brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC,” Ronan Flippot, MD, of Université Paris-Saclay in Villejuif, France, and colleagues wrote in the Journal of Clinical Oncology.

Dr. Flippot and colleagues conducted this analysis of patients from the phase 2 GETUG-AFU 26 NIVOREN trial (NCT03013335). The researchers looked at 73 ccRCC patients with asymptomatic brain metastases who had received at least one prior line of antiangiogenic treatment.

Patients were divided into two cohorts. Cohort A included patients with previously untreated brain metastases (n = 39), and cohort B included patients who had received focal therapy for brain metastases (n = 34).

Baseline characteristics were similar between the cohorts. The median ages were 61 years in cohort A (range, 39-77) and 58 years in cohort B (range, 33-78). Most patients had grade 3-4 tumors (64% in cohort A and 78% in cohort B), and most had one brain lesion (67% and 59%, respectively). The median sum of the diameters of target lesions was 11 mm in cohort A and 17 mm in cohort B.

All patients received intravenous nivolumab at 3 mg/kg every 2 weeks until they progressed, developed unacceptable toxicity, died, withdrew consent, or the investigator stopped treatment.

The median follow-up was 23.6 months in cohort A and 20.2 months in cohort B. The median duration of treatment was 4.9 months and 4.5 months, respectively. Five patients in cohort A and four in cohort B were still receiving nivolumab at the data cutoff.

Response

The primary endpoint was the intracranial response rate in cohort A, which was 12%. All four responders achieved a complete response. At baseline, all of them had grade 1-2 disease and a single brain lesion smaller than 1 cm.

Thirteen patients (38%) in cohort A had stable intracranial disease as their best response, and 17 (50%) had progressive intracranial disease. The remaining five patients could not be evaluated because they progressed and died before the first evaluation.

The extracranial response rate in cohort A was 21%, and all seven responders had partial responses. Ten patients had stable extracranial disease (30%), and 16 had extracranial progression (49%). The remaining six patients were not evaluable for extracranial response.

All four patients who achieved a complete intracranial response had a partial extracranial response. Six patients (18%) had discordant intracranial and extracranial responses.
 

Survival

The median intracranial PFS in cohort A was 2.7 months in cohort A versus 4.8 months in cohort B. When the researchers adjusted for baseline characteristics, they found that prior focal therapy decreased the risk of intracranial progression (hazard ratio, 0.49).

The median extracranial PFS was 2.8 months in cohort A versus 2.6 months in cohort B. The median global PFS was 2.4 months in cohort A versus 2.5 months in cohort B.

The overall survival rates at 12 months were 66.7% in cohort A and 58.8% in cohort B.

Safety

The most common treatment-related adverse events (in cohort A and B, respectively) were asthenia (21% and 24%) and rash (10% and 9%).

Grade 3/4 treatment-related adverse events occurred in four patients in cohort A and five in cohort B. In cohort A, these events were asthenia, elevated liver function tests, dyspnea, and atrioventricular block. In cohort B, the events were diarrhea, musculoskeletal pain, psoriasis, hypophosphatemia, and elevated creatinine (in two patients).

The patient who developed atrioventricular block permanently discontinued nivolumab. There were no other treatment-related adverse events that led to discontinuation.

This study was supported by Bristol-Myers Squibb. The researchers disclosed relationships with Bristol-Myers Squibb and many other companies.

SOURCE: Flippot R et al. J Clin Oncol. 2019 Aug 10;37(23):2008-16.

Nivolumab has “limited intracranial activity” in patients with clear cell renal cell carcinoma (ccRCC) and previously untreated brain metastases, according to researchers.

In a phase 2 trial, nivolumab produced an intracranial response rate of 12% in ccRCC patients with previously untreated brain metastases.

The median intracranial progression-free survival (PFS) was longer among patients who had received prior focal therapy than among those with previously untreated brain metastases.

These results suggest “brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC,” Ronan Flippot, MD, of Université Paris-Saclay in Villejuif, France, and colleagues wrote in the Journal of Clinical Oncology.

Dr. Flippot and colleagues conducted this analysis of patients from the phase 2 GETUG-AFU 26 NIVOREN trial (NCT03013335). The researchers looked at 73 ccRCC patients with asymptomatic brain metastases who had received at least one prior line of antiangiogenic treatment.

Patients were divided into two cohorts. Cohort A included patients with previously untreated brain metastases (n = 39), and cohort B included patients who had received focal therapy for brain metastases (n = 34).

Baseline characteristics were similar between the cohorts. The median ages were 61 years in cohort A (range, 39-77) and 58 years in cohort B (range, 33-78). Most patients had grade 3-4 tumors (64% in cohort A and 78% in cohort B), and most had one brain lesion (67% and 59%, respectively). The median sum of the diameters of target lesions was 11 mm in cohort A and 17 mm in cohort B.

All patients received intravenous nivolumab at 3 mg/kg every 2 weeks until they progressed, developed unacceptable toxicity, died, withdrew consent, or the investigator stopped treatment.

The median follow-up was 23.6 months in cohort A and 20.2 months in cohort B. The median duration of treatment was 4.9 months and 4.5 months, respectively. Five patients in cohort A and four in cohort B were still receiving nivolumab at the data cutoff.

Response

The primary endpoint was the intracranial response rate in cohort A, which was 12%. All four responders achieved a complete response. At baseline, all of them had grade 1-2 disease and a single brain lesion smaller than 1 cm.

Thirteen patients (38%) in cohort A had stable intracranial disease as their best response, and 17 (50%) had progressive intracranial disease. The remaining five patients could not be evaluated because they progressed and died before the first evaluation.

The extracranial response rate in cohort A was 21%, and all seven responders had partial responses. Ten patients had stable extracranial disease (30%), and 16 had extracranial progression (49%). The remaining six patients were not evaluable for extracranial response.

All four patients who achieved a complete intracranial response had a partial extracranial response. Six patients (18%) had discordant intracranial and extracranial responses.
 

Survival

The median intracranial PFS in cohort A was 2.7 months in cohort A versus 4.8 months in cohort B. When the researchers adjusted for baseline characteristics, they found that prior focal therapy decreased the risk of intracranial progression (hazard ratio, 0.49).

The median extracranial PFS was 2.8 months in cohort A versus 2.6 months in cohort B. The median global PFS was 2.4 months in cohort A versus 2.5 months in cohort B.

The overall survival rates at 12 months were 66.7% in cohort A and 58.8% in cohort B.

Safety

The most common treatment-related adverse events (in cohort A and B, respectively) were asthenia (21% and 24%) and rash (10% and 9%).

Grade 3/4 treatment-related adverse events occurred in four patients in cohort A and five in cohort B. In cohort A, these events were asthenia, elevated liver function tests, dyspnea, and atrioventricular block. In cohort B, the events were diarrhea, musculoskeletal pain, psoriasis, hypophosphatemia, and elevated creatinine (in two patients).

The patient who developed atrioventricular block permanently discontinued nivolumab. There were no other treatment-related adverse events that led to discontinuation.

This study was supported by Bristol-Myers Squibb. The researchers disclosed relationships with Bristol-Myers Squibb and many other companies.

SOURCE: Flippot R et al. J Clin Oncol. 2019 Aug 10;37(23):2008-16.

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

Pretreatment CT data may help identify responders to immunotherapy in ovarian cancer, according to a new study.

Specifically, fewer sites of disease and lower intratumor heterogeneity on contrast-enhanced CT may indicate a higher likelihood of durable response to immune checkpoint inhibitors, according to results of the retrospective study, recently published in JCO Precision Oncology.

“Our results suggest that quantitative analysis of baseline contrast-enhanced CT may facilitate the delivery of precision medicine to patients with ovarian cancer by identifying patients who may benefit from immunotherapy,” wrote Yuki Himoto, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues.

The study leverages findings from the emerging field of radiomics, which the investigators note allows for “virtual sampling” of tumor heterogeneity within a single lesion and between lesions.

“This information may complement molecular profiling in personalizing medical decisions,” Dr. Himoto and coauthors explained.

The study cohort included 75 patients with recurrent ovarian cancer who were enrolled in ongoing, prospective trials of immunotherapy, according to the researchers. Of that group, just under one in five derived a durable clinical benefit, defined as progression-free survival lasting at least 24 weeks.

In univariable analysis, they found a number of contrast-enhanced CT variables were linked to durable clinical benefit, including fewer disease sites, lower cluster-site entropy and dissimilarity, which they wrote were an indicator of lower intertumor heterogeneity, and higher energy in the largest-volume lesion, which they described as an indicator of lower intratumor heterogeneity.

However, in multivariable analysis, the only variables that were still associated with durable clinical benefit were fewer disease sites (odds ratio, 1.64; 95% confidence interval, 1.19-2.27; P = .012) and higher energy in the largest lesion (odds ratio, 1.41; 95% CI, 1.11-1.81; P = .006), according to the report.

Those two factors combined were a composite indicator of durable clinical benefit (C-index, 0.821).

These findings could represent a step forward in the provision of immunotherapy in ovarian cancer, which exhibits poor response to immune checkpoint inhibitors, compared with some other cancer types, the investigators wrote.

More insights are needed, however, to help personalize the selection of immunotherapy in ovarian cancer, including a better understanding of cancer immune reactions and retooling of immune response criteria, they added.

“Composite multimodal multifaceted biomarkers that noninvasively capture spatiotemporal tumor heterogeneity will likely be necessary to comprehensively assess immune the tumor microenvironment and serve as clinical decision support for prognosis inference and prediction of response,” Dr. Himoto and associates wrote.

The study was supported by the National Cancer Institute, among other sources. Study authors reported disclosures related to Merck, Bristol-Myers Squibb, Genentech, Celgene, AstraZeneca, Y-mAbs Therapeutics, and others.

SOURCE: Himoto Y et al. JCO Precis Oncol. 2019 Aug 13. doi: 10.1200/PO.19.00038.

Pretreatment CT data may help identify responders to immunotherapy in ovarian cancer, according to a new study.

Specifically, fewer sites of disease and lower intratumor heterogeneity on contrast-enhanced CT may indicate a higher likelihood of durable response to immune checkpoint inhibitors, according to results of the retrospective study, recently published in JCO Precision Oncology.

“Our results suggest that quantitative analysis of baseline contrast-enhanced CT may facilitate the delivery of precision medicine to patients with ovarian cancer by identifying patients who may benefit from immunotherapy,” wrote Yuki Himoto, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues.

The study leverages findings from the emerging field of radiomics, which the investigators note allows for “virtual sampling” of tumor heterogeneity within a single lesion and between lesions.

“This information may complement molecular profiling in personalizing medical decisions,” Dr. Himoto and coauthors explained.

The study cohort included 75 patients with recurrent ovarian cancer who were enrolled in ongoing, prospective trials of immunotherapy, according to the researchers. Of that group, just under one in five derived a durable clinical benefit, defined as progression-free survival lasting at least 24 weeks.

In univariable analysis, they found a number of contrast-enhanced CT variables were linked to durable clinical benefit, including fewer disease sites, lower cluster-site entropy and dissimilarity, which they wrote were an indicator of lower intertumor heterogeneity, and higher energy in the largest-volume lesion, which they described as an indicator of lower intratumor heterogeneity.

However, in multivariable analysis, the only variables that were still associated with durable clinical benefit were fewer disease sites (odds ratio, 1.64; 95% confidence interval, 1.19-2.27; P = .012) and higher energy in the largest lesion (odds ratio, 1.41; 95% CI, 1.11-1.81; P = .006), according to the report.

Those two factors combined were a composite indicator of durable clinical benefit (C-index, 0.821).

These findings could represent a step forward in the provision of immunotherapy in ovarian cancer, which exhibits poor response to immune checkpoint inhibitors, compared with some other cancer types, the investigators wrote.

More insights are needed, however, to help personalize the selection of immunotherapy in ovarian cancer, including a better understanding of cancer immune reactions and retooling of immune response criteria, they added.

“Composite multimodal multifaceted biomarkers that noninvasively capture spatiotemporal tumor heterogeneity will likely be necessary to comprehensively assess immune the tumor microenvironment and serve as clinical decision support for prognosis inference and prediction of response,” Dr. Himoto and associates wrote.

The study was supported by the National Cancer Institute, among other sources. Study authors reported disclosures related to Merck, Bristol-Myers Squibb, Genentech, Celgene, AstraZeneca, Y-mAbs Therapeutics, and others.

SOURCE: Himoto Y et al. JCO Precis Oncol. 2019 Aug 13. doi: 10.1200/PO.19.00038.

Pretreatment CT data may help identify responders to immunotherapy in ovarian cancer, according to a new study.

Specifically, fewer sites of disease and lower intratumor heterogeneity on contrast-enhanced CT may indicate a higher likelihood of durable response to immune checkpoint inhibitors, according to results of the retrospective study, recently published in JCO Precision Oncology.

“Our results suggest that quantitative analysis of baseline contrast-enhanced CT may facilitate the delivery of precision medicine to patients with ovarian cancer by identifying patients who may benefit from immunotherapy,” wrote Yuki Himoto, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues.

The study leverages findings from the emerging field of radiomics, which the investigators note allows for “virtual sampling” of tumor heterogeneity within a single lesion and between lesions.

“This information may complement molecular profiling in personalizing medical decisions,” Dr. Himoto and coauthors explained.

The study cohort included 75 patients with recurrent ovarian cancer who were enrolled in ongoing, prospective trials of immunotherapy, according to the researchers. Of that group, just under one in five derived a durable clinical benefit, defined as progression-free survival lasting at least 24 weeks.

In univariable analysis, they found a number of contrast-enhanced CT variables were linked to durable clinical benefit, including fewer disease sites, lower cluster-site entropy and dissimilarity, which they wrote were an indicator of lower intertumor heterogeneity, and higher energy in the largest-volume lesion, which they described as an indicator of lower intratumor heterogeneity.

However, in multivariable analysis, the only variables that were still associated with durable clinical benefit were fewer disease sites (odds ratio, 1.64; 95% confidence interval, 1.19-2.27; P = .012) and higher energy in the largest lesion (odds ratio, 1.41; 95% CI, 1.11-1.81; P = .006), according to the report.

Those two factors combined were a composite indicator of durable clinical benefit (C-index, 0.821).

These findings could represent a step forward in the provision of immunotherapy in ovarian cancer, which exhibits poor response to immune checkpoint inhibitors, compared with some other cancer types, the investigators wrote.

More insights are needed, however, to help personalize the selection of immunotherapy in ovarian cancer, including a better understanding of cancer immune reactions and retooling of immune response criteria, they added.

“Composite multimodal multifaceted biomarkers that noninvasively capture spatiotemporal tumor heterogeneity will likely be necessary to comprehensively assess immune the tumor microenvironment and serve as clinical decision support for prognosis inference and prediction of response,” Dr. Himoto and associates wrote.

The study was supported by the National Cancer Institute, among other sources. Study authors reported disclosures related to Merck, Bristol-Myers Squibb, Genentech, Celgene, AstraZeneca, Y-mAbs Therapeutics, and others.

SOURCE: Himoto Y et al. JCO Precis Oncol. 2019 Aug 13. doi: 10.1200/PO.19.00038.

A considerable proportion of patients treated with immune checkpoint inhibitors were hospitalized for immune-related toxicities, according to a retrospective cohort study.

In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.

“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.

The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.

The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.

In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.

Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.

“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.

The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.

“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.

Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.

SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.

A considerable proportion of patients treated with immune checkpoint inhibitors were hospitalized for immune-related toxicities, according to a retrospective cohort study.

In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.

“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.

The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.

The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.

In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.

Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.

“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.

The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.

“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.

Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.

SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.

A considerable proportion of patients treated with immune checkpoint inhibitors were hospitalized for immune-related toxicities, according to a retrospective cohort study.

In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.

“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.

The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.

The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.

In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.

Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.

“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.

The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.

“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.

Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.

SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.

Real-world outcome data from patients with advanced non–small cell lung cancer (NSCLC) treated with immunotherapy are robust enough to use for regulatory and payer decisions, suggests an analysis of six data sets and more than 13,000 patients.

“Study of routinely collected health care data is increasingly important for various stakeholders who are interested in better understanding particular patient populations, evaluating drug safety in the postmarketing setting, measuring health care use and clinical outcomes, performing comparative effectiveness research, and optimizing drug pricing models,” noted lead investigator Mark Stewart, PhD, Friends of Cancer Research, Washington, and coinvestigators. “However, before [real-world data] finds widespread use as an adjunct to – or in unique settings, an alternative for – [randomized clinical trials], the validity of readily extractable clinical outcomes measures – real-world endpoints – must be established.”

The investigators undertook a retrospective cohort study using administrative claims and electronic health records for patients with advanced NSCLC treated with inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) between January 2011 and October 2017 in real-world settings. They analyzed six data sets having 269 to 6,924 patients each (13,639 patients total).

Results reported in JCO Clinical Cancer Informatics showed that the real-world intermediate endpoints of time to treatment discontinuation and time to next treatment were moderately to highly correlated with real-world overall survival (Spearman’s rank correlation coefficient, 0.36 to 0.89, with most values 0.60 or higher).

In real-world settings, the 1-year rate of overall survival after starting immunotherapy ranged from 40% to 57%. Real-world data and trial data were similar with respect to median overall survival (8.6-13.5 months vs. 9.2-12.7 months).

The data sources used for the study have been extensively used for research and are curated on an ongoing basis to ensure the data are accurate and as complete as possible, Dr. Stewart and coinvestigators noted.

“These findings demonstrate that real-world endpoints are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision-making,” they maintained. “Differences observed likely reflect true differences between real-world and protocol-driven practices.

“Additional studies are needed to further support the use of [real-world evidence] and inform the development of regulatory guidance,” the investigators concluded. “Standardizing definitions for real-world endpoints and determining appropriate analytic methodologies for [real-world data] will be critical for broader adoption of real-world studies and will provide greater confidence in associated findings. As more refined and standardized approaches are developed that incorporate deep clinical and bioinformatics expertise, the greater the utility of [real-world data] will be for detecting even small, but important, differences in treatment effects.”

Dr. Stewart disclosed no conflicts of interest. The study was supported in part by the National Cancer Institute and the Patient Centered Outcomes Research Institute.

SOURCE: Stewart M et al. JCO Clin Cancer Inform. 2019 July 23. doi: 10.1200/CCI.18.00155.

Real-world outcome data from patients with advanced non–small cell lung cancer (NSCLC) treated with immunotherapy are robust enough to use for regulatory and payer decisions, suggests an analysis of six data sets and more than 13,000 patients.

“Study of routinely collected health care data is increasingly important for various stakeholders who are interested in better understanding particular patient populations, evaluating drug safety in the postmarketing setting, measuring health care use and clinical outcomes, performing comparative effectiveness research, and optimizing drug pricing models,” noted lead investigator Mark Stewart, PhD, Friends of Cancer Research, Washington, and coinvestigators. “However, before [real-world data] finds widespread use as an adjunct to – or in unique settings, an alternative for – [randomized clinical trials], the validity of readily extractable clinical outcomes measures – real-world endpoints – must be established.”

The investigators undertook a retrospective cohort study using administrative claims and electronic health records for patients with advanced NSCLC treated with inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) between January 2011 and October 2017 in real-world settings. They analyzed six data sets having 269 to 6,924 patients each (13,639 patients total).

Results reported in JCO Clinical Cancer Informatics showed that the real-world intermediate endpoints of time to treatment discontinuation and time to next treatment were moderately to highly correlated with real-world overall survival (Spearman’s rank correlation coefficient, 0.36 to 0.89, with most values 0.60 or higher).

In real-world settings, the 1-year rate of overall survival after starting immunotherapy ranged from 40% to 57%. Real-world data and trial data were similar with respect to median overall survival (8.6-13.5 months vs. 9.2-12.7 months).

The data sources used for the study have been extensively used for research and are curated on an ongoing basis to ensure the data are accurate and as complete as possible, Dr. Stewart and coinvestigators noted.

“These findings demonstrate that real-world endpoints are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision-making,” they maintained. “Differences observed likely reflect true differences between real-world and protocol-driven practices.

“Additional studies are needed to further support the use of [real-world evidence] and inform the development of regulatory guidance,” the investigators concluded. “Standardizing definitions for real-world endpoints and determining appropriate analytic methodologies for [real-world data] will be critical for broader adoption of real-world studies and will provide greater confidence in associated findings. As more refined and standardized approaches are developed that incorporate deep clinical and bioinformatics expertise, the greater the utility of [real-world data] will be for detecting even small, but important, differences in treatment effects.”

Dr. Stewart disclosed no conflicts of interest. The study was supported in part by the National Cancer Institute and the Patient Centered Outcomes Research Institute.

SOURCE: Stewart M et al. JCO Clin Cancer Inform. 2019 July 23. doi: 10.1200/CCI.18.00155.

Real-world outcome data from patients with advanced non–small cell lung cancer (NSCLC) treated with immunotherapy are robust enough to use for regulatory and payer decisions, suggests an analysis of six data sets and more than 13,000 patients.

“Study of routinely collected health care data is increasingly important for various stakeholders who are interested in better understanding particular patient populations, evaluating drug safety in the postmarketing setting, measuring health care use and clinical outcomes, performing comparative effectiveness research, and optimizing drug pricing models,” noted lead investigator Mark Stewart, PhD, Friends of Cancer Research, Washington, and coinvestigators. “However, before [real-world data] finds widespread use as an adjunct to – or in unique settings, an alternative for – [randomized clinical trials], the validity of readily extractable clinical outcomes measures – real-world endpoints – must be established.”

The investigators undertook a retrospective cohort study using administrative claims and electronic health records for patients with advanced NSCLC treated with inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) between January 2011 and October 2017 in real-world settings. They analyzed six data sets having 269 to 6,924 patients each (13,639 patients total).

Results reported in JCO Clinical Cancer Informatics showed that the real-world intermediate endpoints of time to treatment discontinuation and time to next treatment were moderately to highly correlated with real-world overall survival (Spearman’s rank correlation coefficient, 0.36 to 0.89, with most values 0.60 or higher).

In real-world settings, the 1-year rate of overall survival after starting immunotherapy ranged from 40% to 57%. Real-world data and trial data were similar with respect to median overall survival (8.6-13.5 months vs. 9.2-12.7 months).

The data sources used for the study have been extensively used for research and are curated on an ongoing basis to ensure the data are accurate and as complete as possible, Dr. Stewart and coinvestigators noted.

“These findings demonstrate that real-world endpoints are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision-making,” they maintained. “Differences observed likely reflect true differences between real-world and protocol-driven practices.

“Additional studies are needed to further support the use of [real-world evidence] and inform the development of regulatory guidance,” the investigators concluded. “Standardizing definitions for real-world endpoints and determining appropriate analytic methodologies for [real-world data] will be critical for broader adoption of real-world studies and will provide greater confidence in associated findings. As more refined and standardized approaches are developed that incorporate deep clinical and bioinformatics expertise, the greater the utility of [real-world data] will be for detecting even small, but important, differences in treatment effects.”

Dr. Stewart disclosed no conflicts of interest. The study was supported in part by the National Cancer Institute and the Patient Centered Outcomes Research Institute.

SOURCE: Stewart M et al. JCO Clin Cancer Inform. 2019 July 23. doi: 10.1200/CCI.18.00155.

Predictors of long-term survival of patients with advanced melanoma, renal cell carcinoma (RCC), non–small cell lung cancer (NSCLC), and other malignancies treated with nivolumab include the absence of liver or bone metastases, excellent baseline performance status, and the presence of grade 3 or greater treatment-related adverse events, investigators have found.

A secondary analysis of the phase 1 CA209-003 trial with expansion cohorts showed that, among 270 heavily pretreated patients with melanoma, RCC, and NSCLC who received single-agent nivolumab (Opdivo) during this trial, those with liver or bone metastases had a 69% higher risk for death within 5 years.

In contrast, patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 had a nearly threefold higher chance for survival, compared with patients with less favorable performance status scores, reported Suzanne L. Topalian, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore and colleagues.

“The results of this study suggest that survival benefits reported in the more limited follow-up of recent nivolumab randomized clinical trials may persist for prolonged periods in some patients, extending to at least 5 years,” they wrote in JAMA Oncology.

In the CA209-003 trial, investigators enrolled patients 18 years or older with documented evidence of advanced melanoma, RCC, NSCLC, castration-resistant prostate cancer, or colorectal cancer. To be eligible, patients needed to have received 1-5 previous systemic therapies for advanced or recurrent cancer, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and an ECOG performance status of 0-2. The current survival analysis included data on 107 patients with melanoma, 34 with RCC, and 129 with NSCLC.

Estimated 5-year overall survival rates were 34.2% for patients with melanoma, 27.7% for patients with RCC, and 15.6% for patients with NSCLC. A multivariable analysis controlling for age, sex, performance status, metastatic disease, and number of prior therapies showed that the presence of either liver or bone metastases was associated with an odds ratio for 5-year survival of 0.31 (P = .02 and .04, respectively).

One factor favorably associated with survival included ECOG performance status 0 (OR, 2.74; P = .003). The investigators also found that treatment-related adverse events (AEs) were associated with longer overall survival, with a median of 19.8 months for patients with any grade of treatment-related event and 20.3 months for patients with grade 3 or greater events, compared with a median of 5.8 months for patients with no treatment-related events (P less than .001 for each comparison based on hazard ratios).

“Of note, patients in our study who developed treatment-related AEs, regardless of whether the AEs were deemed to have an immune-mediated causality, had significantly higher ORRs [overall response rates] and prolonged 5-year OS. These findings are reminiscent of some reports of anti–CTLA-4 therapy and align with other studies of anti–PD-1 therapies, “ Dr. Topalian and associates wrote.

The study and the secondary analysis were supported by Bristol-Myers Squibb. Dr. Topalian disclosed grants and travel reimbursements from Bristol-Myers Squibb and consulting fees with other entities. Multiple co-authors reported similar relationships. Four of the co-authors are Bristol-Myers Squibb employees.

SOURCE: Topalian SL et al. JAMA Oncology. 2019 Jul 25. doi: 10.1001/jamaoncol.2019.2187.

Predictors of long-term survival of patients with advanced melanoma, renal cell carcinoma (RCC), non–small cell lung cancer (NSCLC), and other malignancies treated with nivolumab include the absence of liver or bone metastases, excellent baseline performance status, and the presence of grade 3 or greater treatment-related adverse events, investigators have found.

A secondary analysis of the phase 1 CA209-003 trial with expansion cohorts showed that, among 270 heavily pretreated patients with melanoma, RCC, and NSCLC who received single-agent nivolumab (Opdivo) during this trial, those with liver or bone metastases had a 69% higher risk for death within 5 years.

In contrast, patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 had a nearly threefold higher chance for survival, compared with patients with less favorable performance status scores, reported Suzanne L. Topalian, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore and colleagues.

“The results of this study suggest that survival benefits reported in the more limited follow-up of recent nivolumab randomized clinical trials may persist for prolonged periods in some patients, extending to at least 5 years,” they wrote in JAMA Oncology.

In the CA209-003 trial, investigators enrolled patients 18 years or older with documented evidence of advanced melanoma, RCC, NSCLC, castration-resistant prostate cancer, or colorectal cancer. To be eligible, patients needed to have received 1-5 previous systemic therapies for advanced or recurrent cancer, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and an ECOG performance status of 0-2. The current survival analysis included data on 107 patients with melanoma, 34 with RCC, and 129 with NSCLC.

Estimated 5-year overall survival rates were 34.2% for patients with melanoma, 27.7% for patients with RCC, and 15.6% for patients with NSCLC. A multivariable analysis controlling for age, sex, performance status, metastatic disease, and number of prior therapies showed that the presence of either liver or bone metastases was associated with an odds ratio for 5-year survival of 0.31 (P = .02 and .04, respectively).

One factor favorably associated with survival included ECOG performance status 0 (OR, 2.74; P = .003). The investigators also found that treatment-related adverse events (AEs) were associated with longer overall survival, with a median of 19.8 months for patients with any grade of treatment-related event and 20.3 months for patients with grade 3 or greater events, compared with a median of 5.8 months for patients with no treatment-related events (P less than .001 for each comparison based on hazard ratios).

“Of note, patients in our study who developed treatment-related AEs, regardless of whether the AEs were deemed to have an immune-mediated causality, had significantly higher ORRs [overall response rates] and prolonged 5-year OS. These findings are reminiscent of some reports of anti–CTLA-4 therapy and align with other studies of anti–PD-1 therapies, “ Dr. Topalian and associates wrote.

The study and the secondary analysis were supported by Bristol-Myers Squibb. Dr. Topalian disclosed grants and travel reimbursements from Bristol-Myers Squibb and consulting fees with other entities. Multiple co-authors reported similar relationships. Four of the co-authors are Bristol-Myers Squibb employees.

SOURCE: Topalian SL et al. JAMA Oncology. 2019 Jul 25. doi: 10.1001/jamaoncol.2019.2187.

Predictors of long-term survival of patients with advanced melanoma, renal cell carcinoma (RCC), non–small cell lung cancer (NSCLC), and other malignancies treated with nivolumab include the absence of liver or bone metastases, excellent baseline performance status, and the presence of grade 3 or greater treatment-related adverse events, investigators have found.

A secondary analysis of the phase 1 CA209-003 trial with expansion cohorts showed that, among 270 heavily pretreated patients with melanoma, RCC, and NSCLC who received single-agent nivolumab (Opdivo) during this trial, those with liver or bone metastases had a 69% higher risk for death within 5 years.

In contrast, patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 had a nearly threefold higher chance for survival, compared with patients with less favorable performance status scores, reported Suzanne L. Topalian, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore and colleagues.

“The results of this study suggest that survival benefits reported in the more limited follow-up of recent nivolumab randomized clinical trials may persist for prolonged periods in some patients, extending to at least 5 years,” they wrote in JAMA Oncology.

In the CA209-003 trial, investigators enrolled patients 18 years or older with documented evidence of advanced melanoma, RCC, NSCLC, castration-resistant prostate cancer, or colorectal cancer. To be eligible, patients needed to have received 1-5 previous systemic therapies for advanced or recurrent cancer, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and an ECOG performance status of 0-2. The current survival analysis included data on 107 patients with melanoma, 34 with RCC, and 129 with NSCLC.

Estimated 5-year overall survival rates were 34.2% for patients with melanoma, 27.7% for patients with RCC, and 15.6% for patients with NSCLC. A multivariable analysis controlling for age, sex, performance status, metastatic disease, and number of prior therapies showed that the presence of either liver or bone metastases was associated with an odds ratio for 5-year survival of 0.31 (P = .02 and .04, respectively).

One factor favorably associated with survival included ECOG performance status 0 (OR, 2.74; P = .003). The investigators also found that treatment-related adverse events (AEs) were associated with longer overall survival, with a median of 19.8 months for patients with any grade of treatment-related event and 20.3 months for patients with grade 3 or greater events, compared with a median of 5.8 months for patients with no treatment-related events (P less than .001 for each comparison based on hazard ratios).

“Of note, patients in our study who developed treatment-related AEs, regardless of whether the AEs were deemed to have an immune-mediated causality, had significantly higher ORRs [overall response rates] and prolonged 5-year OS. These findings are reminiscent of some reports of anti–CTLA-4 therapy and align with other studies of anti–PD-1 therapies, “ Dr. Topalian and associates wrote.

The study and the secondary analysis were supported by Bristol-Myers Squibb. Dr. Topalian disclosed grants and travel reimbursements from Bristol-Myers Squibb and consulting fees with other entities. Multiple co-authors reported similar relationships. Four of the co-authors are Bristol-Myers Squibb employees.

SOURCE: Topalian SL et al. JAMA Oncology. 2019 Jul 25. doi: 10.1001/jamaoncol.2019.2187.