Efficacy of Encorafenib/binimetinib in Patients with Metastatic Melanoma with Brain Metastases: Results from the Nationwide Dutch Melanoma Treatment Registry.

9528 Background: Data on the effectiveness of encorafenib plus binimetinib in patients with melanoma brain metastases (BMs) are lacking. Therefore, we aimed to investigate the effectiveness of encorafenib/binimetinib treatment in melanoma patients with BMs. Methods: All melanoma patients with BMs treated with encorafenib/binimetinib between 2019 and 2023 in the Netherlands were included from the nationwide Dutch Melanoma Treatment Registry. Patients with prior BRAF/MEK inhibition treatment were excluded. We analyzed overall response rates (ORR), progression-free (PFS), and overall survival (OS) from start of encorafenib/binimetinib. We performed subgroup analysis for symptomatic versus asymptomatic BMs and previous treatment versus no previous treatment. Results: In total, 208 patients were included. Median age was 61 years and 58.2% of the patients was male. Lactate dehydrogenase levels were elevated in 48.1% of the patients and symptomatic BMs were present in 63.5%. Of all patients, 41.8% received prior immunotherapy and for 58.2% encorafenib/binimetinib was the first-line treatment. The median follow-up duration was 23.2 months. The ORR was 67.3%. Median PFS was 5.6 months (95% confidence interval (CI): 4.9-6.2) and median OS was 10.9 months (95% CI: 9.6-14.0). OS was significantly shorter in patients with symptomatic BMs versus asymptomatic BMs (median 9.7 versus 22.9 months, p<0.01), while PFS was similar (median 5.6 versus 5.8 months, p=0.07). Previously untreated patients had worse prognostic characteristics than previously treated patients. PFS was not significantly different between patients with versus without previous systemic treatment (median 8.8 versus 5.2 months, p=0.08), while OS from start of encorafenib/binimetinib was longer for previously treated patients (median 15.9 versus 9.6 months, p<0.01). Conclusions: Encorafenib plus binimetinib has clinical activity in real world melanoma patients with BMs, but PFS and OS are shorter than previously reported for patients without brain metastases. These data may aid physicians in clinical decision-making.