Treatment of Unresectable Stage III or Metastatic Stage IV Melanoma with BRAF V600 Mutation
Clinical Scenario
BRAF V600 Mutation Confirmed
This protocol addresses patients with unresectable stage III or metastatic stage IV melanoma in whom a BRAF V600 mutation has been identified. Confirmation of this mutation is clinically significant because it expands the set of treatment options available beyond those applicable to BRAF wild-type disease.
Treatment Approach
For BRAF V600-mutated melanoma, the therapeutic options include targeted combination therapy — specifically, a BRAF inhibitor combined with a MEK inhibitor (BRAFi + MEKi) — alongside other established systemic options. The full selection, sequencing, and eligibility criteria for these approaches are detailed in the structured protocol.
References
- In case of BRAF-mutated melanoma, additional first-line options are provided by BRAFis and MEKis.
- 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].
- 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.
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