COMBI-d: dabrafenib and trametinib versus dabrafenib alone for BRAF V600-mutant melanoma
Adding the MEK inhibitor trametinib to the BRAF inhibitor dabrafenib lengthened survival and reduced the skin cancers caused by BRAF inhibition alone in metastatic BRAF-mutant melanoma, establishing dual blockade as the standard for targeted therapy.
Overview
Phase 3 double-blind trial of 423 patients with untreated BRAF V600E or V600K metastatic melanoma randomised to dabrafenib plus trametinib or dabrafenib plus placebo.
Median overall survival was 25.1 versus 18.7 months (hazard ratio 0.71), median progression-free survival 11.0 versus 8.8 months and response 69 versus 53 percent; cutaneous squamous cell carcinomas were fewer with the combination, while pyrexia was more common.
- Median overall survival 25.1 vs 18.7 months; hazard ratio 0.71.
- Objective response 69 percent vs 53 percent.
BRAF plus MEK inhibitor doublets replaced BRAF monotherapy, and dabrafenib-trametinib became the reference regimen for BRAF-mutant melanoma, later extended to adjuvant use in COMBI-AD.
- Pyrexia in over half of combination patients.
- Long-term follow-up shows a plateau of about one third of patients alive at five years.
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