Dabrafenib + trametinib (BRAF/MEK) cuts progression risk in BRAF V600E thyroid cancer

Dabrafenib, a BRAF inhibitor, plus the MEK inhibitor trametinib was tested in a global, randomized, double-blind Phase 3 trial (NCT04940052) in previously treated, radioactive iodine–refractory BRAF V600E–positive differentiated thyroid cancer (n=153). Median PFS was 12.8 months with the combination versus 3.7 months with placebo (HR 0.38, 95%CI 0.25–0.57; p<0.0001), while ORR was 57% versus 4% and median response duration was not reached; OS was not yet significantly improved (HR 0.66; p=0.083). Pyrexia occurred in 48%, serious AEs in 43% versus 25%, and treatment discontinuation in 8% versus 6%; grade≥3 pneumonia occurred in 8%, serous retinopathy in 7%, and one treatment-related fatal stroke was reported. In the same post-VEGFR setting, cabozantinib produced an ORR of approximately 15% and median PFS around 11 months in COSMIC-311, making the 57% response rate here especially notable, although the trials enrolled different molecular populations.