The first phase 3 trial of BRAF/MEK inhibition in radioactive iodine-refractory, BRAF V600E-positive differentiated thyroid cancer, and the results are decisive.
In this global, double-blind trial (153 patients, 42 sites, 11 countries), previously treated patients who had progressed on one or two VEGFR-targeted therapies were randomised 2:1 to dabrafenib plus trametinib or placebo. Dabrafenib plus trametinib more than tripled median progression-free survival , 12.8 vs 3.7 months (HR 0.38, 95% CI 0.25–0.57; p<0.0001), and produced a 57% response rate against 4% on placebo. Interim overall survival favoured the combination but was not yet significant (HR 0.66; p=0.083), immature and confounded by crossover. Pyrexia (48%) and anaemia (45%) were the most common adverse events, with no new safety signals.
We work through what this means for second-line practice, why BRAF genotyping now carries a clear therapeutic consequence, and the limitations, half the cohort from mainland China, and no head-to-head against cabozantinib.
Paper: Gao M, Park YJ, et al. Efficacy and safety of dabrafenib plus trametinib in adults with differentiated thyroid cancer: a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology, 13 July 2026.
https://doi.org/10.1016/S1470-2045(26)00133-6