Encorafenib plus binimetinib in patients with BRAF-mutated melanoma brain metastases: Results from the BECARE (GEM-2002) trial

Abstract

Abstract Background Encorafenib plus binimetinib (EB) is a standard treatment for BRAFV600-mutated melanoma brain metastasis (MBM). However, there is limited evidence of EB use in MBM from clinical trials, and real-world data are scarce. This study aimed to determine the effectiveness and safety of EB in BRAFV600-mutated MBM. Methods BECARE-GEM-2002 was a retrospective study conducted in 24 hospitals in Spain, including patients treated according to standard clinical practice with EB as the 1st line or 2nd line of treatment after progression to immunotherapy, regardless of symptoms and corticosteroid use. Patients had measurable intracranial disease (≥5 mm on CT scan). Previous treatment with BRAF/MEK inhibitors was not allowed. Results Between 2021 and 2025, 60 patients were included, 52 (86.7%) treated upfront and 8 (13.3%) after immune checkpoint inhibitors (ICIs) progression. The ORR was 58.3% (95% confidence interval [CI], 44.9-70.9), 65.4% (95% CI, 44.3-82.8) in asymptomatic, and 52.9% (95% CI, 35.1-70.2) in symptomatic MBM. Radiotherapy (RT) was administered prior to EB in 7 patients (11.7%) and concurrently in 17 (28.3%). Patients receiving RT showed an ORR of 76% (95% CI, 54.9-90.6). The median PFS was 7.4 months (95% CI, 6.2-9.7) and median OS was 10.6 months (95% CI, 9.2-15.0). Treatment-related adverse events of grade ≥3 were reported in 12 patients (20%), the most frequent being transaminitis (6.7%) and gastrointestinal hemorrhage (3.3%). Conclusions EB was safely administered in the real world and showed clinically significant benefit in patients with BRAFV600-mutant MBM, regardless of brain symptoms. The potential role of RT should be explored in prospective trials.