Overall objective responses occurred in one-third of patients with melanoma who were treated with pembrolizumab in a phase 1b clinical trial. The 12-month progression-free survival rate was 35% and the median overall survival was 23 months.1
This phase 1b trial pooled data from 655 enrolled patients to analyze safety and efficacy. The median duration of follow-up was 21 months. The study was performed in medical centers in Australia, Canada, France, and the United States.
Immune system responses to melanoma are limited by the programmed death 1 (PD-1) pathway, which can be blocked by the humanized anti-PD-1 monoclonal antibody pembrolizumab.
This analysis measured objective response rate, which was best overall response of complete or partial response. The objective response rate was 33%.
Median survival was 23 months in the total population (95% CI, 20-29 months) with a 12-month survival rate of 66% (95% CI, 62%-69%) and a 24-month survival rate of 49% (95% CI, 44%-53%). In treatment-naïve patients, median survival was 31 months (95% CI, 24 to not reached), the 12-month survival rate was 73% (95% CI, 65%-79%), and the 24-month survival rate was 60% (95% CI, 51%-68%).
Grade 3 or 4 adverse events occurred in 14% of patients. Treatment was discontinued in 4% of patients because of a treatment-related adverse event. No drug-related deaths occurred.
An accompanying editorial noted that challenges remain for treating metastatic melanoma with a PD-1 blockade.2 Biomarkers need to be identified. The overall efficacy indicates that anti-PD-1 monotherapy has limitations for advanced melanoma, as the 12-month progression-free survival rate was only 35% and even among patients who responded, 26% experienced disease progression.
1.Ribas A, Hamid O, Daud A, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA. 2016;315(15):1600-1609. doi:10.1001/jama.2016.4059.
2. Bhatia S, Thompson JA. PD-1 blockade in melanoma: a promising start, but a long way to go. JAMA. 2016;315(15):1573-1575. doi:10.1001/jama.2016.4012.