First-line pembrolizumab feasible for BRAF V600–mutant melanoma

A recent study recommends the use of pembrolizumab over BRAF/mitogen-activated protein kinase inhibitors, such as dabrafenib/trametinib, as first-line treatment in patients with advanced BRAF V600‒mutant advanced malignant melanoma.

Outcomes related to first-line pembrolizumab or dabrafenib/trametinib treatment for advanced melanoma with activating BRAF V600 mutation were examined. Seventy-two patients with BRAF V600–mutant melanoma had available data for analysis: 40 with first-line pembrolizumab and 32 with dabrafenib/trametinib.

The investigators assessed tumour response, progression-free survival, and overall survival. They also evaluated immune evasion accompanied with emerging resistance to BRAF/mitogen-activated protein kinase inhibitors.

Patients treated with first-line pembrolizumab had longer overall survival than those on first-line dabrafenib/trametinib (hazard ratio, 2.910, 95 percent confidence interval, 1.552‒5.459). However, no significant differences were seen in progression-free survival (p=0.375) and response rate (p=0.123).

“Emergence of resistance to dabrafenib/trametinib co-occurred with immune evasion, enabling melanoma cells to escape recognition and killing by Melan-A–specific CD8⁺ T cells,” the investigators said.

“Pembrolizumab may be recommended over BRAF/mitogen-activated protein kinase kinase inhibitors as the first-line treatment in patients with advanced BRAF V600–mutant melanoma,” they added.

The study was limited by its retrospective nature.

A recent phase III trial investigating the efficacy of spartalizumab in combination with dabrafenib/trametinib did not achieve its primary endpoint of progression-free survival (16.2 months with spartalizumab plus dabrafenib/trametinib vs 12.0 months with placebo plus dabrafenib/trametinib). [J Clin Oncol 2022;40:1428-1438]

“Further biomarker-driven investigation may identify patient subpopulations who could benefit from checkpoint inhibitor plus targeted therapy combinations,” the researchers said.