Clinical outcomes of dabrafenib plus trametinib in locally advanced or metastatic BRAF V600E-mutant papillary thyroid cancer.

Abstract

BRAF V600E is the most common oncogenic mutation in papillary thyroid carcinoma (PTC). This study aimed to assess the clinical outcomes of combining dabrafenib and trametinib in patients with BRAF V600E-mutant PTC. Patients with BRAF V600E-mutant PTC treated with dabrafenib and trametinib in either first-line or second-line settings were included. Dabrafenib was administered orally at 150 mg twice daily, alongside trametinib at 2 mg once daily. Response was determined using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A total of 71 PTC patients who received systemic therapy were identified, including 21 patients who experienced dabrafenib plus trametinib. For these 21 patients, the objective response rate (ORR) was 66.7%, with a disease control rate (DCR) of 85.7%. In the first-line setting, the ORR and DCR were higher at 75.0% and 91.7%, respectively. The median progression-free survival (PFS) was 40.7 months, and the overall survival (OS) was 47.7 months. While patients treated in the first-line setting (n=12) showed better PFS (40.7 months vs. 18.9 months) and OS (47.7 months vs. 39.4 months) compared to those treated in the second-line setting (n=9), the differences were not statistically significant. Moreover, in the first-line treatment, 12 patients received dabrafenib plus trametinib, while 59 patients were treated with lenvatinib; no significant differences in PFS or OS were observed between the two groups. Most adverse events related to the combination therapy were grade 1-2, with no grade 3-4 toxicities reported. Additionally, most patients (75.0%) were able to receive subsequent treatments following disease progression to this combination therapy. The findings of current study highlight the efficacy and safety of dabrafenib combined with trametinib in patients with BRAF V600E-mutant PTC, particularly as a first-line treatment. These findings suggest a promising therapeutic option for this patient population.