OnCo
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Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)

In BRAF-mutant melanoma, start with immunotherapy and keep the targeted pills in reserve; the reverse order costs lives.

DREAMseq: 2-year OS 71.8% vs 51.5% favouring nivolumab-ipilimumab first. Targeted therapy still works after immunotherapy, but immunotherapy after targeted therapy underperforms, possibly because BRAF/MEK progression is rapid and immunologically cold.

Rationale
Immunotherapy responses are durable and can be curative; BRAF/MEK responses are fast but nearly always temporary. Using the durable option first preserves the fast option as a rescue.
Evidence
Phase 3 DREAMseq; phase 2 SECOMBIT concordant.

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