Long-term benefits of pembrolizumab in melanoma

July 28, 2020

A recently published pooled 10-year analysis shows pembrolizumab demonstrates long-term survival benefits for advanced melanoma patients regardless of BRAF V600E/K mutation status or history of BRAFi, with or without MEKi therapy.

Researchers have found pembrolizumab (Keytruda, Merck & Co.) demonstrates long-term survival benefits regardless of BRAF V600E/K mutation status or previous BRAF inhibitor (BRAFi) therapy with or without a MEK inhibitor (MEKi) in metastatic melanoma patients, according to a recently published 10-year analysis in The Journal of American Medical Association Oncology.

The analysis pooled data from three clinical trials (KEYNOTE-001, KEYNOTE-002 and KEYNOTE-006), evaluating a total of 1,558 patients with advanced melanoma who have been treated with pembrolizumab and BRAF tumor status (BRAF wild-type or BRAF V600E/K-mutant melanoma).

Results of the analysis demonstrated an overall response rate (ORR) of 39.8% and 34.3% for BRAF wild-type and BRAF V600E/K-mutant melanoma, respectively, as well as a 4-year progression-free survival (PFS) rate (22.9% and 19.8%) and overall survival (OS) rate (37.5% and 35.1%).

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The study also identified BRAF V600E/K-mutant melanoma patients with history of BRAFi therapy with or without MEKi had baseline characteristics with a lower ORR (28.4% versus 44.2%), 4-year PFS (15.2% vs 27.8%) and OS (26.9% vs 49.3%) versus patients who had no history of targeted therapy.

“Our findings confirmed the long-term, lasting benefits of pembrolizumab for patients with unresectable advanced melanoma and show that the effect is seen regardless of BRAF mutation status — and regardless of earlier treatment with a BRAF-targeting therapy,” says Igor Puzanov, M.D., MSci, FACP, chief of melanoma at Roswell Park Comprehensive Cancer Center and author of the analysis. “Coupled with what we know from separate studies about nivolumab, we see a clear picture of the benefits immune checkpoint inhibitors have had for thousands of people with advanced melanoma over the last decade.”

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This pooled data backs the findings from a January 2020 report from the American Cancer Society, which saw a 7%-per-year decline in overall melanoma deaths from 2013-2017 in patients 20 to 64 years old. The findings also support pembrolizumab as a treatment for advanced melanoma regardless of BRAF V600E/K mutation status or history of BRAFi, with or without MEKi therapy.

“The study reinforces the fact that immunotherapy can significantly extend the life of patients with melanoma and even lead to cures,” says Dr. Puzanov. “But importantly, we also still see a role for targeted therapies. Having both of these treatment options at our disposal has helped to drive incredible progress against [sic] in a cancer type that was almost universally fatal a decade ago.”

An estimated 40% of metastatic melanoma patients also have BRAF mutations, and 90% of those patients have an activating BRAF mutation, according to a press release from Roswell Park.

More information on the study can be found here.

References:

Use of Pembrolizumab Provided Long-Term Benefits in Patients With Metastatic Melanoma, 10-Year Look Shows. (2020, July 16). Retrieved July 28, 2020, from https://www.roswellpark.org/newsroom/202007-use-pembrolizumab-provided-long-term-benefits-patients-metastatic-melanoma-10-year