M Tan1, L Quintal2. 1. Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA. 2. Department of Pharmaceutical Sciences, University of California, San Francisco Medical Center, San Francisco, CA, USA.
Abstract
WHAT IS KNOWN AND OBJECTIVE: To review the pharmacology, efficacy, safety, formulary and economic considerations of pembrolizumab, a novel, first-in-class, anti-PD-1 monoclonal antibody for treatment of advanced melanoma. METHODS: A literature search was conducted using PubMed (July 2013-December 2014) with search terms: pembrolizumab, MK-3475 and lambrolizumab. Additional sources were identified through a subsequent review of all relevant papers, clinicaltrials.gov, product labelling and media releases. All English-language studies conducted in humans with clinical data were included. Review papers were excluded from analysis. RESULTS AND DISCUSSION: Patients with advanced melanoma have limited options available. Immune therapies have shown promise in treating advanced melanoma, but can have significant toxicities. Identification of the role of PD-1 in tumour immune evasion and the subsequent development of pembrolizumab, a novel agent that inhibits PD-1, has led to the availability of an additional treatment option for patients who have progressive disease despite treatment with currently approved agents. Phase I cohort studies have demonstrated promising overall response rates and an estimated progression-free survival of approximately 5·5 months. Minimal toxicity has been observed in patients receiving pembrolizumab, although significant severe immune-mediated reactions have been reported. WHAT IS NEW AND CONCLUSION: Pembrolizumab is a novel anti-PD-1 monoclonal antibody that is an effective option for advanced melanoma previously treated with agents such as ipilimumab and BRAF inhibitors. Additional studies will provide the necessary data for determining its true place in therapy for advanced melanoma and exploring its efficacy in additional malignant indications.
WHAT IS KNOWN AND OBJECTIVE: To review the pharmacology, efficacy, safety, formulary and economic considerations of pembrolizumab, a novel, first-in-class, anti-PD-1 monoclonal antibody for treatment of advanced melanoma. METHODS: A literature search was conducted using PubMed (July 2013-December 2014) with search terms: pembrolizumab, MK-3475 and lambrolizumab. Additional sources were identified through a subsequent review of all relevant papers, clinicaltrials.gov, product labelling and media releases. All English-language studies conducted in humans with clinical data were included. Review papers were excluded from analysis. RESULTS AND DISCUSSION: Patients with advanced melanoma have limited options available. Immune therapies have shown promise in treating advanced melanoma, but can have significant toxicities. Identification of the role of PD-1 in tumour immune evasion and the subsequent development of pembrolizumab, a novel agent that inhibits PD-1, has led to the availability of an additional treatment option for patients who have progressive disease despite treatment with currently approved agents. Phase I cohort studies have demonstrated promising overall response rates and an estimated progression-free survival of approximately 5·5 months. Minimal toxicity has been observed in patients receiving pembrolizumab, although significant severe immune-mediated reactions have been reported. WHAT IS NEW AND CONCLUSION:Pembrolizumab is a novel anti-PD-1 monoclonal antibody that is an effective option for advanced melanoma previously treated with agents such as ipilimumab and BRAF inhibitors. Additional studies will provide the necessary data for determining its true place in therapy for advanced melanoma and exploring its efficacy in additional malignant indications.