Pembrolizumab versus Ipilimumab in Advanced Melanoma

In a multinational, randomized study, pembrolizumab produced significantly improved progression-free and overall survival and less high-grade toxicity than did ipilimumab in patients with metastatic melanoma. Two therapeutic strategies have improved survival for patients with advanced melanoma in recent years: immunotherapy with checkpoint inhibitors and targeted therapies blocking BRAF and MEK. 1 BRAF and MEK inhibitors are indicated for the approximately 40 to 50% of patients with BRAF V600 mutations, 1 whereas immunotherapies are effective independently of BRAF mutational status. 2 Ipilimumab, which blocks cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), a coinhibitory molecule of the immune system, 3 , 4 is approved for treating advanced melanoma on the basis of its survival benefit. 5 , 6 However, grade 3 or 4 adverse events, mostly immune-related, 7 are observed in 23% of patients. 5 , 6 When activated . . .