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. 2016;4(8):867-873.
doi: 10.1080/21678707.2016.1191348. Epub 2016 Jun 7.

Pembrolizumab for the treatment of advanced melanoma

Michael C Burns  1 , Aidan O'Donnell  1 , Igor Puzanov  2
Affiliations

Pembrolizumab for the treatment of advanced melanoma

Michael C Burns et al. Expert Opin Orphan Drugs. 2016.

Abstract

Introduction: Since 2010 multiple targeted therapies and immunotherapies have been approved for the treatment of advanced melanoma. Pembrolizumab, a humanized monoclonal antibody directed against programed death receptor 1 has shown significant activity in advanced melanoma resulting in its approval first as post-ipilimumab and subsequently as frontline treatment.

Areas covered: This article reviews the approved agents for the treatment of advanced melanoma with a focus on the preclinical and clinical evidence for the use of pembrolizumab in this setting. Primary emphasis is given to the clinical development of pembrolizumab, including phase I-III trials. Finally, we explore the role of pembrolizumab in combination with other therapies and ongoing investigations into its effectiveness in expanded patient populations.

Expert opinion: Pembrolizumab provides durable responses and represents a major advancement in the treatment options for patients with advanced melanoma. Early studies of pembrolizumab in combination with other therapeutic agents have generated significant interest and further investigations including advanced clinical trials are warranted to evaluate safety and potential improved outcomes. Pembrolizumab and other immune checkpoint inhibitors are likely to play an expanded role in the treatment of advanced melanoma and other solid tumors over the next decade.

Keywords: immunotherapy; pembrolizumab; programmed death-1; programmed death-ligand 1.

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Conflict of interest statement

Declaration of Interests: The authors have no conflicts of interest to disclose. Declaration of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1
Figure 1
Mechanism of action of pembrolizumab for the treatment of melanoma. T-cell receptor (TCR) signaling is activated when antigenic peptides from cancer cells are presented on major histocompatibility complexes (MHC). TCR signaling results in the expression of the programmed death-1 (PD-1) receptor, which inhibits immune responses when engaged with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2) expressed on cancer cells and antigen presenting cells (APC). Pembrolizumab inhibits the interaction of PD-1 with its ligands resulting in reactivation of the immune system and restoration of the cytotoxic function of tumor-infiltrating lymphocytes.
See this image and copyright information in PMC

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