Pembrolizumab effective in melanoma regardless of BRAF mutation status

Pembrolizumab is effective in advanced melanoma regardless of BRAF mutation status, according to a pooled analysis of long-term outcomes published in JAMA Oncology.

In this post hoc subgroup analysis of pooled data from 3 multinational, multisite studies (KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006), 1558 patients with advanced melanoma and known BRAF V600E/K tumor status who had received pembrolizumab, were included.

The objective response rate, 4-year progression-free survival, and 4-year overall survival (OS) rate were 38.3%, 22.0%, 36.9%, respectively.

In patients with BRAF wild-type ORR was 39.8%, 4-year PFS rate was 22.9, and 4-year OS rate was 37.5%. In patients with BRAF V600E/K-mutant melanoma ORR 34.3%, 4-year PFS rate was 19.8%, and 4-year OS rate was 35.1%.

Compared to patients who had not received prior targeted therapy, patients with BRAF V600E/K-mutant melanoma who had previous experience with BRAF inhibitors had baseline characteristics with worse prognosis.

“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,” said Igor Puzanov, MD, MSci, FACP, Director of Early Phase Clinical Trials and Chief of Melanoma at Roswell Park Comprehensive Cancer Center, and first author of the study, in a statement. “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.”

Reference

Puzanov I, Ribas A, Robert C, et al. Association of BRAF V600E/K Mutation Status and Prior BRAF/MEK Inhibition With Pembrolizumab Outcomes in Advanced Melanoma: Pooled Analysis of 3 Clinical Trials. JAMA Oncol. Published online July 16, 2020. doi:10.1001/jamaoncol.2020.2288