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Immunotherapy with the PD-1 inhibitor pembrolizumab yielded a 33% overall response rate, a 35% progression-free survival rate at 1 year, and a median overall survival of 23 months in 655 patients with advanced melanoma, according to a report published online in JAMA.
The agent generally was well tolerated, with grade 3 or 4 treatment-related toxicities occurring in 14% of patients. Only 4% of patients discontinued pembrolizumab because of adverse events, including colitis, pyrexia, pneumonitis, and thyroid abnormalities, said Dr. Antoni Ribas of University of California, Los Angeles, and his associates.
The investigators analyzed data pooled from 8 open-label phase I cohorts, some of which have been reported previously, in this manufacturer-sponsored study. All the participants were adults (median age, 61 years) with advanced unresectable melanoma who resided in Australia, Canada, France, and the U.S. This pooled study population was heterogeneous, as the various cohorts had different eligibility criteria; some patients were treatment-naïve, some had received ipilimumab, and some were treated concomitantly with BRAF or MEK inhibitors.
The estimated median duration of response was 28.2 months, and 44% of patients who responded to pembrolizumab had a response duration of longer than 1 year. Approximately half of the patients were still alive at 2 years.
Treatment benefit was consistent regardless of whether or not patients had previously received ipilimumab and regardless of the dose or schedule of pembrolizumab they were given. Patients who were treatment-naïve showed the greatest response to pembrolizumab: an overall response rate of 45%, a 1-year progression-free survival rate of 52%, and a median overall survival of 31 months, the investigators said (JAMA. 2016 Apr 19. doi: 10.1001/jama.2016.4059). “Collectively, these data suggest that the majority of patients with melanoma treated with pembrolizumab will experience lasting objective responses,” they added.
The encouraging results of Ribas et al add to the burgeoning literature on the potential of PD-1 blockade to improve outcomes in metastatic melanoma. One finding in particular – the fact that half of the patients in these cohorts were alive at 2 years – is noteworthy because the median overall survival in most previous clinical trials of the disease was consistently shorter than 1 year.
However, the results also highlight the limitations of PD-1 blockade. Median progression-free survival was only 4 months, and the 1-year progression-free survival rate was only 35%. This suggests that the host immune system fails to adequately control the malignancy in two-thirds of patients within the first year. And even among treatment responders, disease progression occurred in 26%.
Dr. Shailender Bhatia and Dr. John A. Thompson are at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle. Dr. Bhatia and Dr. Thompson made these remarks in an editorial accompanying Dr. Ribas’s report (JAMA. 2016 Apr 19;315:1573-4).
The encouraging results of Ribas et al add to the burgeoning literature on the potential of PD-1 blockade to improve outcomes in metastatic melanoma. One finding in particular – the fact that half of the patients in these cohorts were alive at 2 years – is noteworthy because the median overall survival in most previous clinical trials of the disease was consistently shorter than 1 year.
However, the results also highlight the limitations of PD-1 blockade. Median progression-free survival was only 4 months, and the 1-year progression-free survival rate was only 35%. This suggests that the host immune system fails to adequately control the malignancy in two-thirds of patients within the first year. And even among treatment responders, disease progression occurred in 26%.
Dr. Shailender Bhatia and Dr. John A. Thompson are at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle. Dr. Bhatia and Dr. Thompson made these remarks in an editorial accompanying Dr. Ribas’s report (JAMA. 2016 Apr 19;315:1573-4).
The encouraging results of Ribas et al add to the burgeoning literature on the potential of PD-1 blockade to improve outcomes in metastatic melanoma. One finding in particular – the fact that half of the patients in these cohorts were alive at 2 years – is noteworthy because the median overall survival in most previous clinical trials of the disease was consistently shorter than 1 year.
However, the results also highlight the limitations of PD-1 blockade. Median progression-free survival was only 4 months, and the 1-year progression-free survival rate was only 35%. This suggests that the host immune system fails to adequately control the malignancy in two-thirds of patients within the first year. And even among treatment responders, disease progression occurred in 26%.
Dr. Shailender Bhatia and Dr. John A. Thompson are at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle. Dr. Bhatia and Dr. Thompson made these remarks in an editorial accompanying Dr. Ribas’s report (JAMA. 2016 Apr 19;315:1573-4).
Immunotherapy with the PD-1 inhibitor pembrolizumab yielded a 33% overall response rate, a 35% progression-free survival rate at 1 year, and a median overall survival of 23 months in 655 patients with advanced melanoma, according to a report published online in JAMA.
The agent generally was well tolerated, with grade 3 or 4 treatment-related toxicities occurring in 14% of patients. Only 4% of patients discontinued pembrolizumab because of adverse events, including colitis, pyrexia, pneumonitis, and thyroid abnormalities, said Dr. Antoni Ribas of University of California, Los Angeles, and his associates.
The investigators analyzed data pooled from 8 open-label phase I cohorts, some of which have been reported previously, in this manufacturer-sponsored study. All the participants were adults (median age, 61 years) with advanced unresectable melanoma who resided in Australia, Canada, France, and the U.S. This pooled study population was heterogeneous, as the various cohorts had different eligibility criteria; some patients were treatment-naïve, some had received ipilimumab, and some were treated concomitantly with BRAF or MEK inhibitors.
The estimated median duration of response was 28.2 months, and 44% of patients who responded to pembrolizumab had a response duration of longer than 1 year. Approximately half of the patients were still alive at 2 years.
Treatment benefit was consistent regardless of whether or not patients had previously received ipilimumab and regardless of the dose or schedule of pembrolizumab they were given. Patients who were treatment-naïve showed the greatest response to pembrolizumab: an overall response rate of 45%, a 1-year progression-free survival rate of 52%, and a median overall survival of 31 months, the investigators said (JAMA. 2016 Apr 19. doi: 10.1001/jama.2016.4059). “Collectively, these data suggest that the majority of patients with melanoma treated with pembrolizumab will experience lasting objective responses,” they added.
Immunotherapy with the PD-1 inhibitor pembrolizumab yielded a 33% overall response rate, a 35% progression-free survival rate at 1 year, and a median overall survival of 23 months in 655 patients with advanced melanoma, according to a report published online in JAMA.
The agent generally was well tolerated, with grade 3 or 4 treatment-related toxicities occurring in 14% of patients. Only 4% of patients discontinued pembrolizumab because of adverse events, including colitis, pyrexia, pneumonitis, and thyroid abnormalities, said Dr. Antoni Ribas of University of California, Los Angeles, and his associates.
The investigators analyzed data pooled from 8 open-label phase I cohorts, some of which have been reported previously, in this manufacturer-sponsored study. All the participants were adults (median age, 61 years) with advanced unresectable melanoma who resided in Australia, Canada, France, and the U.S. This pooled study population was heterogeneous, as the various cohorts had different eligibility criteria; some patients were treatment-naïve, some had received ipilimumab, and some were treated concomitantly with BRAF or MEK inhibitors.
The estimated median duration of response was 28.2 months, and 44% of patients who responded to pembrolizumab had a response duration of longer than 1 year. Approximately half of the patients were still alive at 2 years.
Treatment benefit was consistent regardless of whether or not patients had previously received ipilimumab and regardless of the dose or schedule of pembrolizumab they were given. Patients who were treatment-naïve showed the greatest response to pembrolizumab: an overall response rate of 45%, a 1-year progression-free survival rate of 52%, and a median overall survival of 31 months, the investigators said (JAMA. 2016 Apr 19. doi: 10.1001/jama.2016.4059). “Collectively, these data suggest that the majority of patients with melanoma treated with pembrolizumab will experience lasting objective responses,” they added.
FROM JAMA
Key clinical point: Immunotherapy with pembrolizumab yielded a 33% overall response rate, a 35% 1-year progression-free survival rate, and a median overall survival of 23 months in 655 patients with advanced melanoma.
Major finding: The estimated median duration of response was 28.2 months, and half of the study population was still alive at 2 years.
Data source: A manufacturer-sponsored pooled analysis of data from 8 open-label phase I cohorts involving 655 patients followed for a median of 15 months.
Disclosures: This study was supported by Merck, maker of pembrolizumab, which also participated in the design and conduct of the study; the collection, analysis, and interpretation of the data; and preparation of the report. Dr. Ribas reported owning stock in several pharmaceutical companies. His associates reported ties to numerous industry sources.
