Authors: Emma D Deeks
Publish Date: 2016/02/04
Volume: 76, Issue: 3, Pages: 375-386
Abstract
Pembrolizumab Keytruda® is a humanized monoclonal antibody against programmed death receptor1 PD1 a key immunoinhibitory checkpoint protein implicated in downregulating antitumour 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 ipilimumabnaïve and/or ipilimumabexperienced 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 progressionfree survival PFS overall survival OS and overall response rates ORR relative to ipilimumab in ipilimumabnaïve patients KEYNOTE 006 and significantly improved PFS and ORR but not OS although OS data are immature relative to chemotherapy in ipilimumabrefractory patients who had also received BRAF/MEK inhibitor therapy if BRAFmutation positive KEYNOTE 002 Pembrolizumab has an acceptable tolerability profile with immunerelated 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
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