DABRAFENIB plus trametinib significantly improved progression free survival and tumour response in patients with radioactive iodine refractory BRAFV600E positive differentiated thyroid cancer, according to findings from a Phase III randomised trial.
The study evaluated the combination in previously treated adults with locally advanced or metastatic disease and demonstrated clinically meaningful benefits compared with placebo, while no new safety signals were identified.
Researchers enrolled 153 previously treated adults from 42 sites across 11 countries between December 2021 and May 2024. Participants had locally advanced or metastatic radioactive iodine refractory BRAFV600E positive differentiated thyroid cancer and were randomly assigned in a 2:1 ratio to receive either dabrafenib plus trametinib or matched placebo.
The primary endpoint was progression free survival, assessed by a blinded independent review committee using Response Evaluation Criteria in Solid Tumors version 1.1.
After a median follow up of 17.4 months, median progression free survival was 12.8 months in the dabrafenib plus trametinib group compared with 3.7 months in the placebo group (hazard ratio:0.38;95% CI:0.25–0.57;p<0.0001). The overall response rate was also substantially higher with the combination therapy at 57% compared with 4% for placebo.
Although an interim analysis suggested a trend towards improved overall survival, statistical significance was not reached (hazard ratio:0.66; 95% CI:0.36–1.19; p=0.083). The median duration of response had not been reached at the time of analysis.
Safety findings were consistent with previous experience of the regimen. Pneumonia was the most frequent grade 3 or higher adverse event, occurring in eight patients receiving dabrafenib plus trametinib and one patient receiving placebo. Serious adverse events of any grade were reported in 43% and 25% of participants in the treatment and placebo groups, respectively. One treatment related death due to cerebrovascular accident occurred in the combination therapy group. Pyrexia was the most commonly reported adverse event, affecting 48% of treated participants. Adverse events leading to treatment discontinuation occurred in 8% of patients receiving dabrafenib plus trametinib and 6% of those receiving placebo.
The investigators concluded that dabrafenib plus trametinib provided significant improvements in progression free survival and overall response rate for patients with radioactive iodine refractory BRAFV600E positive differentiated thyroid cancer who had previously received treatment. Although overall survival data remain immature, the efficacy findings and manageable safety profile support the use of dabrafenib plus trametinib as a second line treatment option for this patient population.
Reference
Gao M et al. Efficacy and safety of dabrafenib plus trametinib in adults with differentiated thyroid cancer: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2026:S1470-2045(26)00133-6.
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