DREAMseq (ECOG-ACRIN EA6134): sequencing dabrafenib-trametinib and nivolumab-ipilimumab in BRAF-mutant metastatic melanoma
Starting with nivolumab plus ipilimumab and switching to BRAF-MEK inhibitors at progression gave 20 percentage points better two-year survival than the reverse order in BRAF-mutant advanced melanoma, settling the question of which to use first.
Overview
Phase 3 trial of 265 patients with treatment-naive BRAF V600-mutant metastatic melanoma randomised to nivolumab-ipilimumab followed by dabrafenib-trametinib at progression, or the reverse sequence.
Two-year overall survival was 71.8 percent with immunotherapy first against 51.5 percent with targeted therapy first; the trial was stopped early for this difference, and responses to immunotherapy were more durable while responses to targeted therapy after immunotherapy were preserved.
- Two-year overall survival 71.8 percent (immunotherapy first) vs 51.5 percent (targeted therapy first).
- Median progression-free survival after crossover favoured targeted therapy given second.
Immunotherapy first is the standard for BRAF-mutant advanced melanoma in patients who can wait for a response; targeted therapy is reserved for rapid control or after immunotherapy.
- Open-label and stopped early.
- Does not address newer first-line options such as nivolumab-relatlimab.
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