title: Pembrolizumab: A Review in Advanced Melanoma.
abstract: Pembrolizumab (Keytruda(®)) is a humanized monoclonal antibody against programmed death receptor-1 (PD-1), a key immunoinhibitory checkpoint protein implicated in down-regulating anti-tumour immune responses. This intravenous drug is indicated for the treatment of advanced (unresectable or metastatic) melanoma, on the basis of its clinical benefit in this setting in the phase I KEYNOTE 001 trial (expansion cohorts) and the phase II and III trials, KEYNOTE 002 and 006. These studies were conducted in ipilimumab-naïve and/or ipilimumab-experienced patients and assessed varying pembrolizumab regimens administered every 2 or 3 weeks, all of which helped to determine the recommended dosage of 2 mg/kg every 3 weeks. In the trials with active comparator arms, pembrolizumab regimens significantly improved progression-free survival (PFS), overall survival (OS) and overall response rates (ORR) relative to ipilimumab in ipilimumab-naïve patients (KEYNOTE 006), and significantly improved PFS and ORR, but not OS (although OS data are immature), relative to chemotherapy in ipilimumab-refractory patients, who had also received BRAF/MEK inhibitor therapy if BRAF-mutation positive (KEYNOTE 002). Pembrolizumab has an acceptable tolerability profile, with immune-related adverse events that are generally manageable/reversible. Thus, pembrolizumab is a valuable treatment option for patients with advanced melanoma, including those who have progressed on ipilimumab and BRAF/MEK inhibitors.
authors: Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. demail@springer.com.
authors: Emma D
authors: ED
authors: Deeks
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D007262:Infusions, Intravenous; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab