Combo.

The SECOMBIT trial demonstrated relative good outcomes with any sequencing of combo ipilimumab/nivolumab and dual BRAF/MEK inhibition for metastatic BRAF-mutated melanoma. The phase 3 DREAMseq trial actually compared various sequencing of ipi/nivo then BRAF/MEKi upon progression [Arm A] or vice versa [Arm B]. The primary endpoint of overall survival at 2 years was much better for Arm A (72%) than Arm B 52%. Interestingly, objective response rates were similar after either initial ipi/nivo (46%) or initial BRAF/MEKi (43)% but starkly different after salvage BRAF/MEKi (48%) versus salvage ipi/nivo (30%). What’s more, there didn’t appear to be any difference in grade 3+ toxicity. In other words, all signs point to starting with combo immune checkpoint inhibition in the initial management of virtually all metastatic melanoma. | Atkins, J Clin Oncol 2022