BRAF/MEK, PD-1 Inhibition May Be Best for BRAF-Mutated Melanoma

Results of a meta-analysis revealed that BRAF/MEK and PD-1 inhibition significantly improved survival in BRAF-mutated melanoma compared with other treatments.

The meta-analysis, conducted by Tahira Devji, BSc, McMaster University, Hamilton, Ontario, and colleagues was designed to provide insight into the most effective first-line systemic treatment options for patients with advanced BRAF-mutated melanoma where head-to-head clinical trial data are lacking.

The review included 15 randomized clinical trials in which at least one intervention was a targeted therapy or an immune checkpoint inhibitor. Data were included from 6,662 patients.

Treatment with either BRAF/MEK targeting agents or PD-1 inhibitors was associated with improved overall survival (OS) benefit compared with all other treatments examined except CTLA-4/granulocyte macrophage colony-stimulating factor (GM-CSF). When comparing these two treatments, the researchers found no significant difference in OS between BRAF/MEK and PD-1 (hazard ratio, 1.02 [95% credible interval, 0.72–1.45]).

“We found that BRAF/MEK and PD-1 inhibitors showed significant survival benefit over all other treatments with the only exception of CTLA-4/GM-CSF therapy where there was no difference in OS,” the researchers wrote in JAMA Oncology. “In our primary and sensitivity analyses of OS, there was no statistically significant difference between BRAF/MEK and PD-1 inhibitors. We therefore conclude that these treatment strategies should be considered equivalent with respect to survival benefit based on current evidence.”

Treatment with BRAF/MEK resulted in significant progression-free survival advantage compared with other treatments. Treatment with PD-1/CTLA-4 had significantly improved progression-free survival compared with PD-1 alone (HR, 0.75) and all other treatments except BRAF/MEK. In addition, BRAF/MEK treatment resulted in higher overall response rates (odds ratio, 2.00 [95% credible interval, 1.64–2.45]) compared with BRAF alone; treatment with BRAF/MEK or BRAF alone had superior overall response rates to any other comparison treatments.

“Survival benefit must be balanced against risk of toxic effects. In the setting of advanced disease, systemic treatment is noncurative for most, and thus quality of life is a priority,” the researchers wrote.

Treatment with chemotherapy and PD-1 inhibitors were associated with the lowest risk for serious adverse events, and there was no significant difference in risk between these two treatment categories.

“Though limited by a sparse network and a lack of OS data for CTLA-4/PD-1, this analysis provides an evidence-based framework to inform clinical decision-making,” the researchers concluded. “Our results show that OS is best with either PD-1 or combined BRAF/MEK inhibition. The favorable safety profile of PD-1 inhibitors supports using this treatment option as first-line therapy in circumstances where rapid response is not a priority.”