1655P Dabrafenib and trametinib in patients with metastatic BRAFV600E-mutated thyroid cancer

Abstract

Papillary thyroid cancer (PTC) is usually treated successfully with surgery and radioactive iodine therapy (RAI), but in some RAI-refractory patients with metastatic and symptomatic disease, systemic therapy could be considered. BRAF mutations are detected in over 80% of PTC in Korea. Dabrafenib plus trametinib showed promising efficacy in patients with metastatic melanoma or non-small cell lung cancer with BRAFV600E mutation. This study evaluated the efficacy and safety of dabrafenib plus trametinib in patients with metastatic BRAFV600E-mutated thyroid cancer. This is a retrospective study of dabrafenib plus trametinib in patients with metastatic BRAFV600E-mutated PTC or PTC with poorly differentiated or anaplastic transformation. Patients had symptomatic disease and progressed in 12 months prior to treatment. Patients received dabrafenib 150mg twice daily and trametinib 2mg once daily as part of the Expanded Access Program at Samsung Medical Center. This study evaluated objective response rate (ORR), safety, and tolerability of dabrafenib plus trametinib. Between December 2019 and January 2022, 25 patients with PTC received dabrafenib plus trametinib (poorly differentiated or anaplastic feature, n=8). Median age was 73.0 years (range, 24-84), the median follow-up was 6.8 months (range, 1.0-28.4). Twenty-two patients received thyroidectomy (3 with initial stage IV) and 8 patients received prior systemic treatment (4 patients with lenvatinib, 3 with sorafenib, 1 with pembrolizumab plus lenvatinib). The median cycle of dabrafenib plus trametinib was 5.9 (range, 1.1-30.4). The site of distant metastasis was lung (n=23), brain (n=3), and bone (n=3). The ORR was 72.0% (18 of PR) and disease control rate was 88.0%. The progression-free survival (PFS) rate at 6 months was 83.6%. Treatment-related adverse events were pyrexia (48.0%), generalized weakness (24.0%), and skin rash (12.0%). Dose reduction due to adverse event was required in 84.0% of patients. Dabrafenib plus trametinib showed high ORR with symptom improvement, however, majority of patients needed dose reduction in patients with BRAFV600E-mutated metastatic PTC. Additional follow-up period is needed for mature data of PFS and overall survival.