Treatment of Amelanocytic Melanoma with BRAF V600 Mutation in Unresectable Stage III–IV Disease
Clinical Scenario
BRAF V600 mutation present
This protocol applies to patients with unresectable stage III or stage IV (metastatic) cutaneous melanoma in whom a BRAF V600 mutation has been identified. The detection of this mutation is central to defining the full scope of therapeutic options.
Therapeutic Approach — Overview
In BRAF V600-mutated melanoma, the range of available treatments extends beyond what is offered for BRAF wild-type disease. Both immunotherapy-based regimens and BRAF pathway-directed combination therapy are within scope, and the appropriate choice depends on prior treatment history and individual patient factors.
The full treatment algorithm — including which options apply, in what order, and under what conditions — is set out in the structured protocol.
References
DOI: 10.1016/j.annonc.2024.11.006
- For BRAF-mutated melanoma, all the options available for BRAF-WT melanoma are still valid, with the addition of combined BRAFi–MEKi therapy if not already used as the immediate prior treatment.
- BRAFi–MEKi therapy after disease progression with first-line immunotherapy should be offered.
- If anti-PD-1-based therapy is not available or patients are considered ineligible for its use, BRAFi–MEKi combination therapy (dabrafenib–trametinib [ESMO-MCBS v1.1 score: 5]; vemurafenib–cobimetinib [ESMO-MCBS v1.1 score: A/5]; binimetinib–encorafenib [ESMO-MCBS v1.1 score: A/5]) is also an option in the first line for patients with BRAF-mutated melanoma [I; A; ESCAT score: I-A].
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