Among patients with BRAF-mutated melanoma, BRAF/MEK and PD-1 inhibition as first-line treatment significantly improved overall survival with PD-1 inhibitors possessing the more favorable safety profile, according to a meta-analysis published in JAMA Oncology.1                      

Although multiple effective first-line systemic treatment options are available for patients with advanced BRAF-mutated melanoma, head-to-head randomized clinical trials comparing targeted therapies and immunotherapies are lacking.

To estimate the relative efficacy and safety of systemic therapeutic options for advanced, treatment-naive, BRAF-mutated melanoma, researchers conducted a systematic review and meta-analysis of phase 2 or 3 randomized controlled trials (RCTs) published up until April 29, 2016. RCTs included at least 1 intervention with a targeted (BRAF or MEK) or an immune checkpoint (cytotoxic T-lymphocyte–associated antigen 4 [CTLA-4] or programmed cell death 1 [PD-1]) inhibitor.

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Analysis of 16 articles reporting 15 RCTs involving a total of 6662 patients showed that both BRAF/MEK and PD-1 inhibitors were associated with improved overall survival compared with all other treatments except anti-CTLA-4 monoclonal antibodies.

Researchers observed no significant difference in overall survival between BRAF/MEK inhibitors and PD-1 inhibitors (hazard ratio, 1.02; 95% CI, 0.72-1.45), though BRAF/MEK inhibition significantly improved progression-free survival compared with all other treatment options.

Treatment with BRAF/MEK inhibition was also associated with a higher objective response rate compared with a BRAF inhibitor alone (odds ratio [OR], 2.00; 95% CI, 1.64-2.45), but both were superior to other treatments with respect to objective response rate.

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Chemotherapy and PD-1 inhibitors were associated with the lowest risk for developing serious adverse events, and there was no significant difference in risk between the 2 strategies (OR, 1.00; 95% CI, 0.74-1.34).

The favorable efficacy and safety profile of PD-1 inhibitors support the use of PD-1 inhibitors as first-line therapy among patients with advanced BRAF-mutated melanoma when rapid response is not a priority.


  1. Devji T, Levine O, Neupane B, et al. Systemic therapy for previously untreated advanced BRAF-mutated melanoma. JAMA Oncology. 2016 Oct 27. doi: 10.1001/jamaoncol.2016.4877 [Epub ahead of print]