This phase 3 randomized study evaluated dabrafenib plus trametinib versus placebo in patients with radioactive iodine-refractory BRAFV600E-positive differentiated thyroid cancer. The combination therapy significantly improved progression-free survival (12.8 months vs 3.7 months) and overall response rate (57% vs 4%) compared to placebo. While an interim analysis for overall survival did not show a statistically significant difference, the safety profile was consistent with previous findings, supporting dabrafenib plus trametinib as a new standard of care in this patient population.
Study
|
Randomised, double-blind, placebo-controlled, phase 3 trial [NCT04940052] |
| Locally advanced or metastatic, radioactive iodine-refractory BRAFV600E-positive differentiated thyroid cancer |
| Dabrafenib plus trametinib (n=101) vs placebo (n=52)
|
Efficacy
|
ORR: 57% vs 4% (stratified difference 53% [42-64], p<0.0001) |
| mPFS: 12.8 mos [10.2-21.2] vs 3.7 mos [2.3-7.5] (HR 0.38 [0.25-0.57], p<0.0001) |
| mOS: Not reached vs 25.9 mos [17.1-NE] (HR 0.66 [0.36-1.19], p=0.083)
|
Safety
|
Grade 3-4 AEs: Pneumonia (8% vs 2%), pyrexia (4% vs 0%), decreased ejection fraction (3% vs 0%), pneumonia bacterial (3% vs 2%), serous retinopathy (7% vs 0%) |
| Serious adverse events: 43% vs 25% |
| Treatment discontinuation due to AE: 8% vs 6%
|
Lancet Oncol 2026;27:994-1003
http://doi.org/10.1016/S1470-2045(26)00133-6
Reviewed by Ulas D. Bayraktar, MD on Aug 20, 2026
