Encorafenib plus binimetinib for BRAF V600-mutated thyroid cancer in Japan: final analysis

Background: The combination of encorafenib plus binimetinib (ENC + BIN) is approved for the treatment of BRAF V600-mutated thyroid cancer in Japan, based on a phase 2 trial. We update the efficacy and safety data for ENC + BIN of this phase 2 trial after prolonged follow-up. Methods: This multicenter, open-label, uncontrolled phase 2 trial evaluated the efficacy and safety of ENC + BIN in patients with unresectable locally advanced or metastatic BRAF V600-mutated thyroid cancer that was not amenable to curative treatment, who were refractory/intolerant to ≥ 1 previous vascular endothelial growth factor receptor-targeted regimens, or were considered ineligible for these. The primary endpoint was the objective response rate (ORR). The secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: We enrolled 22 patients: 17 with differentiated thyroid carcinoma (DTC) and 5 with anaplastic thyroid carcinoma (ATC). During a prolonged period with a median follow-up of 28.7 months (range: 3.4–40.6), 3 additional patients with DTC achieved partial responses, increasing the ORR to 68.2% (15/22 patients with either DTC or ATC). Medians for PFS and OS were not reached for DTC and 17.7 and 24.3 months, respectively, for ATC. Common adverse events were eye disorder (5/12), infections and infestations (4/12), and skin and subcutaneous tissue disorder (4/12) after > 360 days; no new safety signals were identified during the extended follow-up period. Conclusions: With a > 24-month median follow-up, this analysis indicates that ENC + BIN provides sustained tumor responses in patients with BRAF V600-mutated thyroid cancer. The long-term safety profile is consistent with previous reports.