Renal Cell Carcinoma

SAN FRANCISCO – Two immune checkpoint inhibitors that help restore the antitumor response are active and well tolerated in patients with advanced, generally heavily pretreated gastric and esophageal cancers, according to a pair of early-phase trials reported at the Gastrointestinal Cancers Symposium.

Results from CheckMate-032 showed that nivolumab, an antibody that targets the cell surface receptor programmed death-1 (PD-1), yielded a response rate of 14% in patients with advanced gastric and related cancers. And updated results from KEYNOTE-028 showed that pembrolizumab, another antibody targeting PD-1, led to a response rate of 30% in patients with advanced esophageal and related cancers that expressed the ligand programmed death ligand 1 (PD-L1).

“Checkpoint inhibitors are clearly promising new agents ... All compounds are still in development, but we already have at least phase 1 data that they are effective,” commented invited discussant Dr. Markus H. Möhler of the University Medical Center Mainz (Germany). “Combination treatment strategies are clearly under investigation, and it is our task as a scientific community to look into interesting modern combinations, like combinations with antiangiogenic agents or maybe even with stem cell inhibition.”

He commended the KEYNOTE-028 investigators, in particular, for their development of a tumor gene signature that appeared to predict benefit from pembrolizumab.

“Molecular and immunological characterization of the patients is key, and we have seen now in the pembrolizumab study with the six-gene signature the first step in the right direction,” Dr. Möhler said, recommending that it be correlated with data from The Cancer Genome Atlas project, which has identified four distinct molecular subtypes of esophagogastric cancer.

“It is now clear that some of these subtypes express higher PD-L1 compared to the others, particularly inflamed subtypes,” he elaborated. “Therefore, it is clear that all the studies in the future really should try to look into the correlation with these four gene subgroups characterized.”

CheckMate-032 trial

Patients with a variety of solid tumors were eligible for CheckMate-032, a phase I/II trial. First author Dr. Dung T. Le reported results for 59 patients with locoregionally advanced or metastatic gastric cancer, esophageal, or gastroesophageal junction cancer who had received at least one prior therapy.

The patients were treated with nivolumab (Opdivo) every 2 weeks. (Nivolumab is currently FDA approved for the treatment of melanoma, non–small cell lung cancer, and renal cancer.)

With a median follow-up of 4.6 months, the response rate was 14%, reported Dr. Le of Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, at the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.

However, “PD-L1 expression appears to be numerically associated with a higher objective response rate,” she noted. Specifically, the response rate was 27% among patients whose tumor cells showed 1% or greater PD-L1 staining, and an even higher 33% among those whose tumor cells showed 5% or greater PD-L1 staining.

Median overall survival was 5 months. The 6-month overall survival rate was 49%, and the 12-month rate was 36%.

“The adverse event profile was similar to that seen in patients with other tumor types,” Dr. Le commented.

In all, 17% of patients experienced grade 3 or 4 treatment-related adverse events, and 5% experienced grade 3 or 4 treatment-related serious adverse events. These events included elevation of liver enzymes, pneumonitis, fatigue, diarrhea, and vomiting. There were no treatment-related deaths.

KEYNOTE-028 trial

Patients with various types of advanced solid tumors were eligible for KEYNOTE-028, a phase Ib trial, if at least 1% of their tumor or inflammatory cells expressed PD-L1. First author Dr. Toshihiko Doi reported results for 23 patients with esophageal or gastroesophageal junction cancer who had experienced failure of standard therapy or were unable to tolerate it.

The patients were treated with pembrolizumab (Keytruda) every 2 weeks. (Pembrolizumab is currently FDA approved for the treatment of melanoma and non–small cell lung cancer.)

With a median follow-up of 7.1 months, the overall response rate was 30%, reported Dr. Doi of the National Cancer Center Hospital East in Chiba, Japan. By tumor histology, it was 29% for squamous cell carcinomas and 40% for adenocarcinomas.

He and his colleagues performed gene expression profiling of tumor tissue, identifying a six-gene interferon gamma signature that appeared predictive.

Specifically, patients with high signature scores, indicating more inflamed tumors, tended to have a better response rate than those with low scores (43% vs. 11%) as well as longer progression-free survival.

In all, 17% of patients experienced grade 3 treatment-related adverse events (reduced appetite, lymphopenia, liver disorder, and pruritic rash). There were no treatment-related deaths or discontinuations. With respect to adverse events of special interest because of their immune etiology, 9% of patients experienced hypothyroidism, 4% adrenal insufficiency, and 4% pruritic rash.

“Further evaluation of pembrolizumab in esophageal cancer is ongoing,” Dr. Doi concluded, pointing to the KEYNOTE-180 trial, which is testing the agent as third-line therapy, and the KEYNOTE-181 trial, which is pitting it against treatment of physician’s choice as second-line therapy.

SAN FRANCISCO – Two immune checkpoint inhibitors that help restore the antitumor response are active and well tolerated in patients with advanced, generally heavily pretreated gastric and esophageal cancers, according to a pair of early-phase trials reported at the Gastrointestinal Cancers Symposium.

Results from CheckMate-032 showed that nivolumab, an antibody that targets the cell surface receptor programmed death-1 (PD-1), yielded a response rate of 14% in patients with advanced gastric and related cancers. And updated results from KEYNOTE-028 showed that pembrolizumab, another antibody targeting PD-1, led to a response rate of 30% in patients with advanced esophageal and related cancers that expressed the ligand programmed death ligand 1 (PD-L1).

“Checkpoint inhibitors are clearly promising new agents ... All compounds are still in development, but we already have at least phase 1 data that they are effective,” commented invited discussant Dr. Markus H. Möhler of the University Medical Center Mainz (Germany). “Combination treatment strategies are clearly under investigation, and it is our task as a scientific community to look into interesting modern combinations, like combinations with antiangiogenic agents or maybe even with stem cell inhibition.”

He commended the KEYNOTE-028 investigators, in particular, for their development of a tumor gene signature that appeared to predict benefit from pembrolizumab.

“Molecular and immunological characterization of the patients is key, and we have seen now in the pembrolizumab study with the six-gene signature the first step in the right direction,” Dr. Möhler said, recommending that it be correlated with data from The Cancer Genome Atlas project, which has identified four distinct molecular subtypes of esophagogastric cancer.

“It is now clear that some of these subtypes express higher PD-L1 compared to the others, particularly inflamed subtypes,” he elaborated. “Therefore, it is clear that all the studies in the future really should try to look into the correlation with these four gene subgroups characterized.”

CheckMate-032 trial

Patients with a variety of solid tumors were eligible for CheckMate-032, a phase I/II trial. First author Dr. Dung T. Le reported results for 59 patients with locoregionally advanced or metastatic gastric cancer, esophageal, or gastroesophageal junction cancer who had received at least one prior therapy.

The patients were treated with nivolumab (Opdivo) every 2 weeks. (Nivolumab is currently FDA approved for the treatment of melanoma, non–small cell lung cancer, and renal cancer.)

With a median follow-up of 4.6 months, the response rate was 14%, reported Dr. Le of Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, at the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.

However, “PD-L1 expression appears to be numerically associated with a higher objective response rate,” she noted. Specifically, the response rate was 27% among patients whose tumor cells showed 1% or greater PD-L1 staining, and an even higher 33% among those whose tumor cells showed 5% or greater PD-L1 staining.

Median overall survival was 5 months. The 6-month overall survival rate was 49%, and the 12-month rate was 36%.

“The adverse event profile was similar to that seen in patients with other tumor types,” Dr. Le commented.

In all, 17% of patients experienced grade 3 or 4 treatment-related adverse events, and 5% experienced grade 3 or 4 treatment-related serious adverse events. These events included elevation of liver enzymes, pneumonitis, fatigue, diarrhea, and vomiting. There were no treatment-related deaths.

KEYNOTE-028 trial

Patients with various types of advanced solid tumors were eligible for KEYNOTE-028, a phase Ib trial, if at least 1% of their tumor or inflammatory cells expressed PD-L1. First author Dr. Toshihiko Doi reported results for 23 patients with esophageal or gastroesophageal junction cancer who had experienced failure of standard therapy or were unable to tolerate it.

The patients were treated with pembrolizumab (Keytruda) every 2 weeks. (Pembrolizumab is currently FDA approved for the treatment of melanoma and non–small cell lung cancer.)

With a median follow-up of 7.1 months, the overall response rate was 30%, reported Dr. Doi of the National Cancer Center Hospital East in Chiba, Japan. By tumor histology, it was 29% for squamous cell carcinomas and 40% for adenocarcinomas.

He and his colleagues performed gene expression profiling of tumor tissue, identifying a six-gene interferon gamma signature that appeared predictive.

Specifically, patients with high signature scores, indicating more inflamed tumors, tended to have a better response rate than those with low scores (43% vs. 11%) as well as longer progression-free survival.

In all, 17% of patients experienced grade 3 treatment-related adverse events (reduced appetite, lymphopenia, liver disorder, and pruritic rash). There were no treatment-related deaths or discontinuations. With respect to adverse events of special interest because of their immune etiology, 9% of patients experienced hypothyroidism, 4% adrenal insufficiency, and 4% pruritic rash.

“Further evaluation of pembrolizumab in esophageal cancer is ongoing,” Dr. Doi concluded, pointing to the KEYNOTE-180 trial, which is testing the agent as third-line therapy, and the KEYNOTE-181 trial, which is pitting it against treatment of physician’s choice as second-line therapy.

SAN FRANCISCO – Two immune checkpoint inhibitors that help restore the antitumor response are active and well tolerated in patients with advanced, generally heavily pretreated gastric and esophageal cancers, according to a pair of early-phase trials reported at the Gastrointestinal Cancers Symposium.

Results from CheckMate-032 showed that nivolumab, an antibody that targets the cell surface receptor programmed death-1 (PD-1), yielded a response rate of 14% in patients with advanced gastric and related cancers. And updated results from KEYNOTE-028 showed that pembrolizumab, another antibody targeting PD-1, led to a response rate of 30% in patients with advanced esophageal and related cancers that expressed the ligand programmed death ligand 1 (PD-L1).

“Checkpoint inhibitors are clearly promising new agents ... All compounds are still in development, but we already have at least phase 1 data that they are effective,” commented invited discussant Dr. Markus H. Möhler of the University Medical Center Mainz (Germany). “Combination treatment strategies are clearly under investigation, and it is our task as a scientific community to look into interesting modern combinations, like combinations with antiangiogenic agents or maybe even with stem cell inhibition.”

He commended the KEYNOTE-028 investigators, in particular, for their development of a tumor gene signature that appeared to predict benefit from pembrolizumab.

“Molecular and immunological characterization of the patients is key, and we have seen now in the pembrolizumab study with the six-gene signature the first step in the right direction,” Dr. Möhler said, recommending that it be correlated with data from The Cancer Genome Atlas project, which has identified four distinct molecular subtypes of esophagogastric cancer.

“It is now clear that some of these subtypes express higher PD-L1 compared to the others, particularly inflamed subtypes,” he elaborated. “Therefore, it is clear that all the studies in the future really should try to look into the correlation with these four gene subgroups characterized.”

CheckMate-032 trial

Patients with a variety of solid tumors were eligible for CheckMate-032, a phase I/II trial. First author Dr. Dung T. Le reported results for 59 patients with locoregionally advanced or metastatic gastric cancer, esophageal, or gastroesophageal junction cancer who had received at least one prior therapy.

The patients were treated with nivolumab (Opdivo) every 2 weeks. (Nivolumab is currently FDA approved for the treatment of melanoma, non–small cell lung cancer, and renal cancer.)

With a median follow-up of 4.6 months, the response rate was 14%, reported Dr. Le of Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, at the symposium, which was sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.

However, “PD-L1 expression appears to be numerically associated with a higher objective response rate,” she noted. Specifically, the response rate was 27% among patients whose tumor cells showed 1% or greater PD-L1 staining, and an even higher 33% among those whose tumor cells showed 5% or greater PD-L1 staining.

Median overall survival was 5 months. The 6-month overall survival rate was 49%, and the 12-month rate was 36%.

“The adverse event profile was similar to that seen in patients with other tumor types,” Dr. Le commented.

In all, 17% of patients experienced grade 3 or 4 treatment-related adverse events, and 5% experienced grade 3 or 4 treatment-related serious adverse events. These events included elevation of liver enzymes, pneumonitis, fatigue, diarrhea, and vomiting. There were no treatment-related deaths.

KEYNOTE-028 trial

Patients with various types of advanced solid tumors were eligible for KEYNOTE-028, a phase Ib trial, if at least 1% of their tumor or inflammatory cells expressed PD-L1. First author Dr. Toshihiko Doi reported results for 23 patients with esophageal or gastroesophageal junction cancer who had experienced failure of standard therapy or were unable to tolerate it.

The patients were treated with pembrolizumab (Keytruda) every 2 weeks. (Pembrolizumab is currently FDA approved for the treatment of melanoma and non–small cell lung cancer.)

With a median follow-up of 7.1 months, the overall response rate was 30%, reported Dr. Doi of the National Cancer Center Hospital East in Chiba, Japan. By tumor histology, it was 29% for squamous cell carcinomas and 40% for adenocarcinomas.

He and his colleagues performed gene expression profiling of tumor tissue, identifying a six-gene interferon gamma signature that appeared predictive.

Specifically, patients with high signature scores, indicating more inflamed tumors, tended to have a better response rate than those with low scores (43% vs. 11%) as well as longer progression-free survival.

In all, 17% of patients experienced grade 3 treatment-related adverse events (reduced appetite, lymphopenia, liver disorder, and pruritic rash). There were no treatment-related deaths or discontinuations. With respect to adverse events of special interest because of their immune etiology, 9% of patients experienced hypothyroidism, 4% adrenal insufficiency, and 4% pruritic rash.

“Further evaluation of pembrolizumab in esophageal cancer is ongoing,” Dr. Doi concluded, pointing to the KEYNOTE-180 trial, which is testing the agent as third-line therapy, and the KEYNOTE-181 trial, which is pitting it against treatment of physician’s choice as second-line therapy.

A novel approach to oncologic surveillance after surgical resection for renal cell carcinoma (RCC) that incorporates patient age, Charlson comorbidity index, pathologic tumor stage, and relapse location–specific data, may provide better recommendations for surveillance duration than current guidelines, researchers reported.

“By providing more individualized recommendations and by eliminating oversimplified time thresholds for surveillance, this strategy, we believe, represents an improvement over current guidelines,” wrote Dr. Suzanne Stewart-Merrill of the department of urology, Mayo Clinic, Rochester, Minn., and colleagues (J Clin Oncol. 2015 Sep 7. doi: 10.1200/JCO.2015.61.8009).

©Wikimedia Commons/Patho/Public Domain

Guidelines suggest surveillance durations based on cumulative incidence of recurrences, but do not account for individual patient risk factors. Adherence to the guidelines could miss up to one-third of all recurrences, the authors noted. The longest surveillance duration advocated by the National Comprehensive Cancer Network or the American Urological Association is 5 years.

Researchers used Weibull models for risk of recurrence, stratified by stage and relapse location, combined with risk estimates for non-RCC death, to estimate the optimum surveillance duration. For example, for patients aged 50-59 years with pT1Nx-0 disease and a Charlson comorbidity index of less than or equal to 1, risk of non-RCC death exceeded the risk of abdominal recurrence at 7 years, marking the recommended surveillance duration for that subgroup. The recommended surveillance duration for patients with similar characteristics aged 60-69 years is 2.5 years, and for patients aged 70-79 years it is 1.5 years.

When taking into account individual risk factors, the method produced a wide range of surveillance durations. For patients under 50 years old with pT1Nx-0 disease and a Charlson comorbidity index less than or equal to 1, the risk of non-RCC death did not exceed the risk of abdominal recurrence for more than 20 years. By contrast, patients with pT1Nx-0 disease and Charlson comorbidity index greater than or equal to 2, had a higher risk of non-RCC death than risk of abdominal recurrence at 30 days after surgery.

The retrospective study of 2,511 patients who underwent surgical resection for M0 sporadic RCC between 1990 and 2008 had a median follow up of 9.0 years (interquartile range 6.4-12.7 years).

The researchers noted that recurrences beyond 5 years are fairly common, with up to 15% of patients, by one study’s estimate, experiencing recurrence during the decade following surgery. Cumulative incidence of recurrence does not capture how a patient’s risk of recurrence changes with time or how comorbid conditions influence risk.

The proposed surveillance method results in shorter surveillance durations for some patients and longer surveillance durations than currently recommended for others. This diversity in stopping points “better reflects the range of disease courses appreciated in patients with RCC on the basis of the interplay that occurs between the risk of recurrence and other competing health factors,” Dr. Stewart-Merrill and associates explained.

Dr. Stewart-Merrill reported having no disclosures.

A novel approach to oncologic surveillance after surgical resection for renal cell carcinoma (RCC) that incorporates patient age, Charlson comorbidity index, pathologic tumor stage, and relapse location–specific data, may provide better recommendations for surveillance duration than current guidelines, researchers reported.

“By providing more individualized recommendations and by eliminating oversimplified time thresholds for surveillance, this strategy, we believe, represents an improvement over current guidelines,” wrote Dr. Suzanne Stewart-Merrill of the department of urology, Mayo Clinic, Rochester, Minn., and colleagues (J Clin Oncol. 2015 Sep 7. doi: 10.1200/JCO.2015.61.8009).

©Wikimedia Commons/Patho/Public Domain

Guidelines suggest surveillance durations based on cumulative incidence of recurrences, but do not account for individual patient risk factors. Adherence to the guidelines could miss up to one-third of all recurrences, the authors noted. The longest surveillance duration advocated by the National Comprehensive Cancer Network or the American Urological Association is 5 years.

Researchers used Weibull models for risk of recurrence, stratified by stage and relapse location, combined with risk estimates for non-RCC death, to estimate the optimum surveillance duration. For example, for patients aged 50-59 years with pT1Nx-0 disease and a Charlson comorbidity index of less than or equal to 1, risk of non-RCC death exceeded the risk of abdominal recurrence at 7 years, marking the recommended surveillance duration for that subgroup. The recommended surveillance duration for patients with similar characteristics aged 60-69 years is 2.5 years, and for patients aged 70-79 years it is 1.5 years.

When taking into account individual risk factors, the method produced a wide range of surveillance durations. For patients under 50 years old with pT1Nx-0 disease and a Charlson comorbidity index less than or equal to 1, the risk of non-RCC death did not exceed the risk of abdominal recurrence for more than 20 years. By contrast, patients with pT1Nx-0 disease and Charlson comorbidity index greater than or equal to 2, had a higher risk of non-RCC death than risk of abdominal recurrence at 30 days after surgery.

The retrospective study of 2,511 patients who underwent surgical resection for M0 sporadic RCC between 1990 and 2008 had a median follow up of 9.0 years (interquartile range 6.4-12.7 years).

The researchers noted that recurrences beyond 5 years are fairly common, with up to 15% of patients, by one study’s estimate, experiencing recurrence during the decade following surgery. Cumulative incidence of recurrence does not capture how a patient’s risk of recurrence changes with time or how comorbid conditions influence risk.

The proposed surveillance method results in shorter surveillance durations for some patients and longer surveillance durations than currently recommended for others. This diversity in stopping points “better reflects the range of disease courses appreciated in patients with RCC on the basis of the interplay that occurs between the risk of recurrence and other competing health factors,” Dr. Stewart-Merrill and associates explained.

Dr. Stewart-Merrill reported having no disclosures.

A novel approach to oncologic surveillance after surgical resection for renal cell carcinoma (RCC) that incorporates patient age, Charlson comorbidity index, pathologic tumor stage, and relapse location–specific data, may provide better recommendations for surveillance duration than current guidelines, researchers reported.

“By providing more individualized recommendations and by eliminating oversimplified time thresholds for surveillance, this strategy, we believe, represents an improvement over current guidelines,” wrote Dr. Suzanne Stewart-Merrill of the department of urology, Mayo Clinic, Rochester, Minn., and colleagues (J Clin Oncol. 2015 Sep 7. doi: 10.1200/JCO.2015.61.8009).

©Wikimedia Commons/Patho/Public Domain

Guidelines suggest surveillance durations based on cumulative incidence of recurrences, but do not account for individual patient risk factors. Adherence to the guidelines could miss up to one-third of all recurrences, the authors noted. The longest surveillance duration advocated by the National Comprehensive Cancer Network or the American Urological Association is 5 years.

Researchers used Weibull models for risk of recurrence, stratified by stage and relapse location, combined with risk estimates for non-RCC death, to estimate the optimum surveillance duration. For example, for patients aged 50-59 years with pT1Nx-0 disease and a Charlson comorbidity index of less than or equal to 1, risk of non-RCC death exceeded the risk of abdominal recurrence at 7 years, marking the recommended surveillance duration for that subgroup. The recommended surveillance duration for patients with similar characteristics aged 60-69 years is 2.5 years, and for patients aged 70-79 years it is 1.5 years.

When taking into account individual risk factors, the method produced a wide range of surveillance durations. For patients under 50 years old with pT1Nx-0 disease and a Charlson comorbidity index less than or equal to 1, the risk of non-RCC death did not exceed the risk of abdominal recurrence for more than 20 years. By contrast, patients with pT1Nx-0 disease and Charlson comorbidity index greater than or equal to 2, had a higher risk of non-RCC death than risk of abdominal recurrence at 30 days after surgery.

The retrospective study of 2,511 patients who underwent surgical resection for M0 sporadic RCC between 1990 and 2008 had a median follow up of 9.0 years (interquartile range 6.4-12.7 years).

The researchers noted that recurrences beyond 5 years are fairly common, with up to 15% of patients, by one study’s estimate, experiencing recurrence during the decade following surgery. Cumulative incidence of recurrence does not capture how a patient’s risk of recurrence changes with time or how comorbid conditions influence risk.

The proposed surveillance method results in shorter surveillance durations for some patients and longer surveillance durations than currently recommended for others. This diversity in stopping points “better reflects the range of disease courses appreciated in patients with RCC on the basis of the interplay that occurs between the risk of recurrence and other competing health factors,” Dr. Stewart-Merrill and associates explained.

Dr. Stewart-Merrill reported having no disclosures.

After a median follow-up of 45 months, the anti–PD-1 antibody nivolumab showed benefit in a majority of patients who had previously received one to five treatments for renal cell carcinoma, according to a report published online March 23 in the Journal of Clinical Oncology.

The previously treated cohort included 71% who had received two prior systemic treatments and 44% who had received three or more prior treatments for renal cell carcinoma (RCC). Out of the total 34 patients, 10 (29%) had objective responses, nine (27%) had stable disease for at least 24 weeks, 2 (6%) had stable disease for at least 48 weeks, and 3 patients (9%) had unconventional immune-related responses, which can include reduction in target lesions in the presence of new lesions or regression after initial progression (J. Clin. Oncol. 2015 Mar. 23 [doi:10.1200/JCO.2014.58.1041]).

“The results of our study suggest that nivolumab can be administered safely in an outpatient setting to pretreated patients with RCC and demonstrate durable clinical activity. Blockade of the PD-1 pathway may represent an important new target for RCC therapy,” wrote Dr. David F. McDermott of Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, and his colleagues.

Adverse events of any grade were experienced by 29 (85%) patients, and 6 patients had grade 3-4 events. The toxicities, the most frequent of which were fatigue (14), rash (9), diarrhea (6), and pruritus (6), were consistent with immune-related mechanisms. The investigators noted that the favorable safety profile may permit the antibody to be used in combination and adjuvant regimens.

Patients received intravenous nivolumab 1 mg/kg (18 patients) or 10 mg/kg (16 patients) in an outpatient setting twice per week for up to 96 weeks. Some degree of tumor shrinkage occurred in 20 of 34 patients. Among the 10 patients with objective responses, the median duration was 12.9 months (range, 8.4-29.1+ months, with four responses ongoing at the time of analysis). Overall survival rates at 1, 2, and 3 years were 71%, 48%, and 44%, respectively, and the median overall survival was 22.4 months.

While the results are encouraging, the authors added that more research to understand the mechanism of action is needed to optimize the use of anti–PD-1 antibodies. Studies have shown that tumor expression of PD-L1 increases the likelihood of benefit from anti–PD-1, but not in all cases.

“A more comprehensive understanding of why some patients with PD-L1–negative tumors respond to PD-1 pathway blockade, while many with PD-L1–positive tumors fail to do so, will be critical to improving patient selection and developing anti–PD-1–based combination strategies for RCC,” they wrote.

Dr. McDermott reported having consulting or advisory roles with Bristol-Myers Squibb, Merck, Genentech/Roche, and Pfizer. Many of his coauthors reported ties to several industry sources.

After a median follow-up of 45 months, the anti–PD-1 antibody nivolumab showed benefit in a majority of patients who had previously received one to five treatments for renal cell carcinoma, according to a report published online March 23 in the Journal of Clinical Oncology.

The previously treated cohort included 71% who had received two prior systemic treatments and 44% who had received three or more prior treatments for renal cell carcinoma (RCC). Out of the total 34 patients, 10 (29%) had objective responses, nine (27%) had stable disease for at least 24 weeks, 2 (6%) had stable disease for at least 48 weeks, and 3 patients (9%) had unconventional immune-related responses, which can include reduction in target lesions in the presence of new lesions or regression after initial progression (J. Clin. Oncol. 2015 Mar. 23 [doi:10.1200/JCO.2014.58.1041]).

“The results of our study suggest that nivolumab can be administered safely in an outpatient setting to pretreated patients with RCC and demonstrate durable clinical activity. Blockade of the PD-1 pathway may represent an important new target for RCC therapy,” wrote Dr. David F. McDermott of Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, and his colleagues.

Adverse events of any grade were experienced by 29 (85%) patients, and 6 patients had grade 3-4 events. The toxicities, the most frequent of which were fatigue (14), rash (9), diarrhea (6), and pruritus (6), were consistent with immune-related mechanisms. The investigators noted that the favorable safety profile may permit the antibody to be used in combination and adjuvant regimens.

Patients received intravenous nivolumab 1 mg/kg (18 patients) or 10 mg/kg (16 patients) in an outpatient setting twice per week for up to 96 weeks. Some degree of tumor shrinkage occurred in 20 of 34 patients. Among the 10 patients with objective responses, the median duration was 12.9 months (range, 8.4-29.1+ months, with four responses ongoing at the time of analysis). Overall survival rates at 1, 2, and 3 years were 71%, 48%, and 44%, respectively, and the median overall survival was 22.4 months.

While the results are encouraging, the authors added that more research to understand the mechanism of action is needed to optimize the use of anti–PD-1 antibodies. Studies have shown that tumor expression of PD-L1 increases the likelihood of benefit from anti–PD-1, but not in all cases.

“A more comprehensive understanding of why some patients with PD-L1–negative tumors respond to PD-1 pathway blockade, while many with PD-L1–positive tumors fail to do so, will be critical to improving patient selection and developing anti–PD-1–based combination strategies for RCC,” they wrote.

Dr. McDermott reported having consulting or advisory roles with Bristol-Myers Squibb, Merck, Genentech/Roche, and Pfizer. Many of his coauthors reported ties to several industry sources.

After a median follow-up of 45 months, the anti–PD-1 antibody nivolumab showed benefit in a majority of patients who had previously received one to five treatments for renal cell carcinoma, according to a report published online March 23 in the Journal of Clinical Oncology.

The previously treated cohort included 71% who had received two prior systemic treatments and 44% who had received three or more prior treatments for renal cell carcinoma (RCC). Out of the total 34 patients, 10 (29%) had objective responses, nine (27%) had stable disease for at least 24 weeks, 2 (6%) had stable disease for at least 48 weeks, and 3 patients (9%) had unconventional immune-related responses, which can include reduction in target lesions in the presence of new lesions or regression after initial progression (J. Clin. Oncol. 2015 Mar. 23 [doi:10.1200/JCO.2014.58.1041]).

“The results of our study suggest that nivolumab can be administered safely in an outpatient setting to pretreated patients with RCC and demonstrate durable clinical activity. Blockade of the PD-1 pathway may represent an important new target for RCC therapy,” wrote Dr. David F. McDermott of Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, and his colleagues.

Adverse events of any grade were experienced by 29 (85%) patients, and 6 patients had grade 3-4 events. The toxicities, the most frequent of which were fatigue (14), rash (9), diarrhea (6), and pruritus (6), were consistent with immune-related mechanisms. The investigators noted that the favorable safety profile may permit the antibody to be used in combination and adjuvant regimens.

Patients received intravenous nivolumab 1 mg/kg (18 patients) or 10 mg/kg (16 patients) in an outpatient setting twice per week for up to 96 weeks. Some degree of tumor shrinkage occurred in 20 of 34 patients. Among the 10 patients with objective responses, the median duration was 12.9 months (range, 8.4-29.1+ months, with four responses ongoing at the time of analysis). Overall survival rates at 1, 2, and 3 years were 71%, 48%, and 44%, respectively, and the median overall survival was 22.4 months.

While the results are encouraging, the authors added that more research to understand the mechanism of action is needed to optimize the use of anti–PD-1 antibodies. Studies have shown that tumor expression of PD-L1 increases the likelihood of benefit from anti–PD-1, but not in all cases.

“A more comprehensive understanding of why some patients with PD-L1–negative tumors respond to PD-1 pathway blockade, while many with PD-L1–positive tumors fail to do so, will be critical to improving patient selection and developing anti–PD-1–based combination strategies for RCC,” they wrote.

Dr. McDermott reported having consulting or advisory roles with Bristol-Myers Squibb, Merck, Genentech/Roche, and Pfizer. Many of his coauthors reported ties to several industry sources.