First-Line Treatment of Unresectable or Metastatic Cutaneous Melanoma with BRAF V600 Mutation
This protocol covers patients with cutaneous melanoma that is unresectable and/or metastatic, in whom molecular testing has confirmed a BRAF V600 mutation. The mutation status is a key determinant of which first-line systemic treatment pathways are available.
Clinical scenario: Cutaneous melanoma, confirmed unresectable or metastatic, with a BRAF V600 mutation identified on molecular testing. Multiple distinct first-line treatment strategies apply to this population.
First-Line Approach
For this population, first-line treatment involves a choice between immune checkpoint inhibitor combinations and BRAF/MEK-targeted regimens — with combination immunotherapy generally preferred as the initial approach. The complete list of options, preferred sequence, and supporting evidence are in the full protocol.
References
- For patients with BRAF mutant (V600) unresectable and/or metastatic cutaneous melanoma, one of the following treatment options should be offered as first-line therapy: nivolumab plus ipilimumab followed by nivolumab OR nivolumab plus relatlimab OR nivolumab OR pembrolizumab OR dabrafenib plus trametinib OR encorafenib plus binimetinib OR vemurafenib plus cobimetinib.
- Combination therapy with nivolumab plus ipilimumab is preferred as first-line therapy over BRAF/MEK inhibitor combination therapy.
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