Pembrolizumab is a humanized high-affinity antibody that exerts dual-ligand blockade of the immune checkpoint receptor programmed death-1 (PD-1). The KEYNOTE-001 trial is a phase 1 nonrandomized dose-escalation trial that tested pembrolizumab in 5 dose/schedule cohorts that included 135 ipilimumab-naïve (IPI-N) and IPI-treated (IPI-T) patients. A pooled analysis of the 5 cohorts showed an overall response rate (ORR) of 34%, with higher responses achieved in the IPI-N subgroup versus the IPI-T subgroup (40% vs 28%, respectively). Based on no unfavorable safety signals, the treatment cohort was then expanded to include 276 patients with IPI-N- and IPI-refractory disease who were randomized to receive MK-3475 10 mg/kg or 2 mg/kg every 3 weeks. At ESMO 2014, the efficacy and safety of pembrolizumab 10 mg/kg every 3 weeks and 10 mg/kg every 2 weeks in patients enrolled in a randomized expansion cohort of KEYNOTE-001 trial were reported (Robert C, et al. KEYNOTE-001 Trial. ESMO 2014: Abstract LBA34). A total of 244 patients were enrolled in the 2 dose-expansion cohorts of 10 mg/kg every 3 weeks (N = 121) and 10 mg/kg every 2 weeks (N = 123), with 123 and 121 patients in the IPI-N and IPI-T groups. The safety analysis showed that treatment-related adverse events were similar between the 2 dose cohorts; common toxicities included fatigue (38%), pruritus (23%), and diarrhea (18%). At a median follow-up of 42.3 weeks, 70% of patients in the every 3 weeks cohort and 57% in the every 2 weeks cohort achieved a decrease in target-lesion size compared with baseline. In the total population, ORR by RECIST criteria was 33%, including a 5% complete response rate. There were no significant differences in ORR between the 2 dose schedules (P = .5052) or based on previous ipilimumab use. No between-schedule differences in progression-free survival (PFS) were reported; median PFS was 13.1 weeks and 22.6 weeks in the every 3 weeks and every 2 weeks cohorts. Robert and colleagues concluded that the response rates, PFS, and safety were comparable between the 2 pembrolizumab 10 mg/kg every 3 weeks and 10 mg/kg every 2 weeks treatment schedule cohorts, and support the use of the recently approved dose and schedule of pembrolizumab 2 mg/kg every 3 weeks in patients with advanced melanoma.
