Choosing Between Triplet Therapy and Immunotherapy in BRAF-Mutant Melanoma

Dirk Schadendorf, MD, professor of dermatology and oncology and director of the Department of Dermatology and the West German Cancer Center at University Hospital Essen in Germany, spoke with CancerNetwork® about how clinicians might select first-line treatment for patients with BRAF V600–mutant melanoma in light of final data from the phase 3 STARBOARD trial (NCT04657991), presented at the 2026 European Society for Medical Oncology (ESMO) Congress. STARBOARD evaluated encorafenib (Braftovi), binimetinib (Mektovi), and pembrolizumab (Keytruda) vs placebo plus pembrolizumab and showed a median progression-free survival of 33.0 months with the triplet vs 3.4 months with pembrolizumab alone.

Schadendorf said that any patient being considered for BRAF/MEK-targeted therapy should now also be considered for the triplet, highlighting symptomatic disease and fast tumor kinetics as key factors. He described the regimen as an alternative to nivolumab (Opdivo) plus ipilimumab (Yervoy) in this setting. For patients with brain metastases, he noted that dual checkpoint blockade remains the standard at most centers, but that the triplet should be considered when comorbidities, autoimmunity, or prior checkpoint inhibitor failure rule that approach out.

Transcript:

Schadendorf: When we are deciding which patients should get targeted therapy and which patients should get checkpoint blockade, there is a group of patients for whom we consider targeted therapy, and all these patients, I believe, should now also be considered candidates for triplet therapy. Whether you should use BRAF/MEK inhibition on its own, without checkpoint blockade, is the big question, because given the magnitude of the PFS benefit, we have not seen a comparable median PFS in any of the BRAF/MEK clinical trials. Patients who have symptomatic disease or fast tumor kinetics are candidates for the triplet, and it is a perfect alternative to nivolumab and ipilimumab, which would usually be considered in such a situation. In BRAF V600–mutant melanoma, I now believe this could be a good alternative.

Brain metastases are a challenge. In most centers, dual checkpoint blockade with nivolumab and ipilimumab is the standard of care for patients with brain metastases. If that is not feasible because of comorbidities, autoimmunity, or prior failure of checkpoint blockade, then in patients with BRAF V600–mutant melanoma, triplet therapy can be considered and, in my view, should be considered.

Reference

Schadendorf D, Dummer R, Sullivan RJ, et al. STARBOARD phase 3: a randomized, double-blind study of first-line encorafenib, binimetinib, and pembrolizumab vs placebo and pembrolizumab for unresectable locally advanced or metastatic BRAF V600-mutant melanoma. Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract 2071O.