Incumbent.

Top Line: With two great options, what should come first in the treatment of metastatic BRAF-mutant melanoma?

The Study: The international phase 2 SECOMBIT trial randomized 209 treatment-naive patients with metastatic BRAF-mutant melanoma to one of three arms: [1] dual BRAF/MEK inhibition until progression and then combo ipi/nivo, [2] combo ipi/nivo until progression and then dual BRAF/MEK inhibition, or [3] dual BRAF/MEK inhibition for 8 weeks only and then combo ipi/nivo until progression and then dual BRAF/MEK inhibition. Whew. Importantly, this wasn’t designed to compare outcomes across arms but rather to assess outcomes in each arm as compared to historical controls. The primary endpoint of overall survival rates at 2 years were [1] 65%, [2] 73%, and [3] 69% and at 3 years was [1] 54%, [2] 62%, and [3] 60%. In other words, all arms were success stories. The question is which success story is the best first-line approach?

TBL: It’s still not a bad strategy to typically start with immunotherapy even for BRAF-mutated melanoma.  | Ascierto, J Clin Oncol 2022