This protocol covers patients with unresectable stage III or metastatic (stage IV) cutaneous amelanocytic melanoma in whom a BRAF V600 mutation has been confirmed — a clinically important sub-population where molecular status directly determines the treatment pathway.
Unresectable stage III or stage IV (metastatic) cutaneous melanoma with a confirmed BRAF V600 mutation. This mutation status is a key stratification criterion and shapes which therapeutic approaches are available at each line of treatment.
BRAF V600 mutation-positiveThe protocol for this scenario involves a structured rechallenge strategy: selecting between a targeted therapy class or an immune-based approach according to what was administered in the prior treatment line. Where neither class is accessible or feasible, an alternative systemic option may be considered as a later-line measure.
DOI: 10.1016/j.annonc.2024.11.006
If anti-PD-1-based therapy is not available or patients are considered ineligible for its use, BRAFieMEKi combination therapy (dabrafenibetrametinib [ESMO-MCBS v1.1 score: 5]; vemurafenibecobimetinib [ESMO-MCBS v1.1 score: A/5]; binimetinibeencorafenib [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].
Third-line treatment rechallenge with the drug class (BRAFieMEKi [IV, C] or ICI [IV, B]) not used in the immediate previous line can be considered, if feasible.
If clinical trials, ICIs or BRAFis/MEKis are not available, ChT may be administered as later-line therapy [IV, C], with modest activity and no impact on OS.