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Pembrolizumab: A Review in Advanced Melanoma

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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.

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Acknowledgments

During the peer review process, the manufacturer of pembrolizumab was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Emma D. Deeks

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  1. Emma D. Deeks
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Correspondence to Emma D. Deeks.

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The preparation of this review was not supported by any external funding.

Conflicts of interest

Emma Deeks is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: A. Jalili, Department of Dermatology, Medical University of Vienna, Vienna, Austria; E. C. Jones, Department of Dermatology, Stony Brook University, Stony Brook, NY, USA.

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Deeks, E.D. Pembrolizumab: A Review in Advanced Melanoma. Drugs 76, 375–386 (2016). https://doi.org/10.1007/s40265-016-0543-x

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