Just give it.

There’s an age-old (ok, few years-old) question of what to give first for advanced melanoma: BRAF/MEK inhibitors or immune checkpoint inhibitors. This pooled analysis of of 1558 patients enrolled on three large KEYNOTE studies of pembrolizumab for melanoma asked whether outcomes differed based on prior exposure to BRAFi with or without MEKi. Overall, neither response rate (RR), progression-free survival (PFS) nor overall survival (OS) differed based on whether the patient was BRAF wildtype (n=1124) or mutant (n=434). As one might expect, those who failed prior BRAF/MEKi had worse disease characteristics. As such, prior BRAF/MEKi was associated with significantly worse RR, PFS, and OS, even across subgroup and multivariate analyses. TBL: While this Merck-funded publication recognizes melanoma refractory to BRAF/MEKi is less likely to respond to subsequent pembro—and clearly everyone should be getting pembro first-line, anyway—giving pembro second-line is still worth it to achieve a response rate in roughly a quarter of patients. | Puzanov, JAMA Oncol 2020