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.
Dr. Antoni Ribas
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.