Survival outcomes in radioactive iodine-refractory (RAIR) differentiated thyroid cancer (DTC) with BRAF mutation: A real-world study from the Spanish Taskforce for Neuroendocrine and Endocrine Tumors (GETNE) Thyroid Cancer registry.

Abstract

e18159 Background: For BRAF V600E RAIR-DTC, the role of BRAF with or without MEK inhibitors (BRAFi; MEKi) has been studied, given the success of these therapies in other solid tumors. Although BRAFi + MEKi are FDA-approved for BRAF-mutated solid tumors, their role in RAIR-DTC remains underexplored, particularly outside the U.S. This real-world study, aims to compare oncological outcomes of BRAF V600E RAIR-DTC patients treated or not with BRAFi. Methods: Data from the Spanish GETNE thyroid cancer registry were analyzed, comprising 345 DTC patients. Categorical variables were compared using the chi-square test. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier and alternative log-rank tests. Results: Out of 345 DTC patients included in the registry, 173 had known BRAF status, and 84 (48.5%) were BRAF-mutated. A total of 59 patients with RAIR disease that had initiated systemic treatment were included: 24 patients received BRAFi and 35 did not, during their disease course. Papillary thyroid cancer was the most common histological subtype (95%). BRAF-targeted therapy was administered as first-line (1L) treatment in 79% of patients and included Dabrafenib + Trametinib (50%), Dabrafenib monotherapy (25%), and Vemurafenib monotherapy (4%). Patients treated with BRAFi were more likely to receive third and fourth lines of treatment compared to untreated patients (p=0.08 and p=0.009, respectively). Median overall survival (OS) was 83 months (CI 95% 73-91 months) in patients treated with BRAFi versus 71 (CI 95% 34-115 months) months in those untreated (p=0.17). Median progression free survival (PFS) was 17 months (CI 95% 14-32 months) for patients receiving BRAFi (+/- MEKi) as first-line treatment and 16 months (CI 95% 11-20 months) for those receiving tyrosine kinase inhibitors (TKIs; mainly Lenvatinib 51% and Sorafenib 40%) (p=0.33). Conclusions: Patients treated with BRAFi showed numerically longer OS (83 vs. 71 months) and comparable PFS in 1L (17 vs. 16 months) compared to TKIs, supporting its potential as an effective option in this setting. These findings underscore the potential of BRAFi to improve long-term outcomes in RAIR-DTC patients with BRAF mutations and support its integration into treatment algorithms with caution due to the lack of validation in prospective randomized studies. This study is one of the first comparing outcomes of BRAF V600E RAIR-DTC patients treated or not with BRAFi.