Immunotherapy or molecularly targeted therapy: what is the best initial treatment for stage IV BRAF-mutant melanoma?

The recent developments in BRAF-targeted therapy and checkpoint inhibitor immunotherapies for metastatic melanoma patients have led to better tolerability and markedly improved clinical outcomes, including higher objective response rates and longer survival. Treatment planning has become complex in patients with metastatic BRAF-mutant melanoma, with several options for BRAF- and/or MEK-targeted therapy (vemurafenib, dabrafenib, and trametinib) and immunotherapy (interleukin 2, ipilimumab, pembrolizumab, and nivolumab). Clinicians must weigh various patient factors, including the extent of disease (eg, symptomatic visceral metastases vs limited disease) and central nervous system involvement, as well as factors related to the therapeutic agent, such as rate of clinical response, durability of response, and impact on median and long-term survival. The combination regimen of dabrafenib plus trametinib has become a standard treatment strategy, and ipilimumab plus nivolumab is emerging as a promising treatment strategy. In this review, we discuss the benchmark trials leading to the approval of these new agents and provide emerging data on their use in sequence and impact on overall survival, with the goal of helping oncologists navigate treatment decisions for patients with metastatic BRAF-mutant melanoma.