Pembrolizumab versus Ipilimumab in Advanced Melanoma

• Published in: The New England journal of medicine Vol. 372; no. 26; pp. 2521 - 2532
• Main Authors: Robert, Caroline, Schachter, Jacob, Long, Georgina V, Arance, Ana, Grob, Jean Jacques, Mortier, Laurent, Daud, Adil, Carlino, Matteo S, McNeil, Catriona, Lotem, Michal, Larkin, James, Lorigan, Paul, Neyns, Bart, Blank, Christian U, Hamid, Omid, Mateus, Christine, Shapira-Frommer, Ronnie, Kosh, Michele, Zhou, Honghong, Ibrahim, Nageatte, Ebbinghaus, Scot, Ribas, Antoni
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 25.06.2015
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antitumor activity; Apoptosis; Body weight; Cell death; Chemotherapy; Drug dosages; Equity stake; Fees & charges; Female; Humans; Immune checkpoint inhibitors; Immune system; Immunotherapy; Ipilimumab; Laboratories; Male; Melanoma; Melanoma - drug therapy; Melanoma - mortality; Middle Aged; Monoclonal antibodies; Mutation; Patients; PD-1 protein; Pembrolizumab; Programmed Cell Death 1 Receptor - immunology; Response rates; Skin Neoplasms - drug therapy; Skin Neoplasms - mortality; Survival Analysis; Toxicity; Tumors; Young Adult
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1503093

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 . . .