Pembrolizumab versus Ipilimumab in Advanced Melanoma.

Abstract (PubMed)

The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks. Primary end points were progression-free and overall survival. The estimated 6-month progression-free-survival rates were 47.3% for pembrolizumab every 2 weeks, 46.4% for pembrolizumab every 3 weeks, and 26.5% for ipilimumab (hazard ratio for disease progression, 0.58; P<0.001 for both pembrolizumab regimens versus ipilimumab). Estimated 12-month survival rates were 74.1%, 68.4%, and 58.2%, respectively. Response rates were 33.7% and 32.9% for the two pembrolizumab doses versus 11.9% for ipilimumab. Adverse events of grade 3 to 5 attributed to the study drugs occurred in 13.3%, 10.1%, and 19.9% of patients in the three groups. Pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than ipilimumab.