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Pembrolizumab for Advanced Melanoma: Impact of BRAF-Mutation Status and Prior Therapeutic Regimens


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In a pooled analysis reported in JAMA Oncology, Igor Puzanov, MD, MSCI, and colleagues identified objective response rates and progression-free and overall survival rates with pembrolizumab treatment among patients with advanced melanoma according to BRAF V600E/K–mutation status and prior BRAF/MEK inhibitor therapy.

Igor Puzanov, MD, MSCI

Igor Puzanov, MD, MSCI

Study Details

The post hoc subgroup analysis included 1,558 patients from the KEYNOTE-001, -002, and -006 trials who received pembrolizumab at 2 mg/kg every 3 weeks, 10 mg/kg every 2 weeks, or 10 mg/kg every 3 weeks for advanced melanoma. Analysis included outcomes according to BRAF wild-type and BRAF V600E/K–mutant status, and according to whether patients with BRAF-mutant disease did or did not receive prior BRAF inhibitor therapy with or without MEK inhibitor therapy.

Key Findings

Among all patients, objective response rate was 38.3%, the 4-year progression-free survival was 22.0%, and the 4-year overall survival was 36.9%.

For patients with BRAF wild-type (n = 1,124) and patients with BRAF V600E/K–mutant melanoma (n = 434), objective response rates were 39.8% vs 34.3%, 4-year progression-free survival was 22.9% vs 19.8%, and 4-year overall survival was 37.5% vs 35.1%.

Among patients with BRAF V600E/K–mutant melanoma, those who had received prior BRAF inhibitor therapy with or without MEK inhibitor therapy (n = 271) had higher rates of baseline factors known to be associated with poorer outcome in patients with melanoma vs those who had not received prior BRAF inhibitors with or without MEK inhibitors (n = 163), including PD-L1–negative tumors, elevated lactate dehydrogenase, poorer performance status, and larger tumors.

For those without vs with prior BRAF inhibitor therapy with or without MEK inhibitor therapy, objective response rates were 44.2% vs 28.4%, 4-year progression-free survival was 27.8% vs 15.2%, and 4-year overall survival was 49.3% vs 26.9%.

The investigators concluded, “Results of this subgroup analysis support the use of pembrolizumab for treatment of advanced melanoma regardless of BRAF V600E/K mutation status or receipt of prior BRAF inhibitor therapy with or without MEK inhibitor therapy.”

Dr. Puzanov, of Roswell Park Cancer Institute, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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