Dabrafenib Plus Trametinib Shows Significant Clinical Benefit in BRAF V600E-Mutated Thyroid Cancer
Results from a phase 3 trial demonstrated that dabrafenib plus trametinib significantly improved survival and response rates among patients with BRAF V600E-mutated, radioiodine-refractory thyroid cancer.
These findings were presented by Lori Wirth, MD, Massachusetts General Hospital, Boston, Massachusetts, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
In this double-blind study, 153 patients who had received prior vascular endothelial growth factor receptor (VEGFR)–targeted therapy were randomized 2:1 to receive either dabrafenib plus trametinib or placebo. Crossover from the placebo arm was permitted after centrally confirmed disease progression.
The primary end point was progression-free survival (PFS). Key secondary end points included objective response rate (ORR), overall survival (OS), and safety.
At analysis, the median PFS was 12.8 months in the dabrafenib plus trametinib arm and 3.7 months in the placebo arm (hazard ratio [HR], 0.38; 95% CI, 0.25 to 0.57; P <.001). The ORR was 54.7% in dabrafenib plus trametinib arm and 3.8% in the placebo arm (P <.001). Median OS was not reached in the dabrafenib plus trametinib arm. Although OS favored dabrafenib plus trametinib, the difference did not reach statistical significance (P = .083).
The most common adverse events included pyrexia (47.5%) and anemia (44.6%). The most frequently reported treatment-related serious adverse event was pyrexia (3%), and serious retinopathy occurred in 6.9% of patients.
As Dr Wirth concluded, “[dabrafenib plus trametinib] combination therapy demonstrated a significant benefit in PFS and ORR… [and] safety results were consistent with the well-established safety profile.”
Source:
Wirth L, Gao M, Park YJ, et al. Efficacy and safety of dabrafenib plus trametinib (D+T) in patients with radioactive iodine (RAI)–refractory BRAF V600–mutant differentiated thyroid cancer (DTC). Presented at the 2025 European Society for Medical Oncology (ESMO) Congress; October 17–21, 2025; Berlin, Germany. Abstract 2987O.
