Encorafenib and binimetinib followed by radiotherapy for patients with symptomatic BRAF mutated melanoma brain metastases: GEM1802/E-BRAIN clinical trial

Patients (pts) with symptomatic melanoma brain metastases (MBM) have very poor prognosis. For BRAF mutated (mut) targeted therapy achieves high intracranial response rate (iRR) but intracranial progression free survival (iPFS) is usually short. With immunotherapy iRR can be long lasting in asymptomatic pts but are less frequent in symptomatic ones, especially if they need steroids GEM1802/EBRAIN (NCT03898908) evaluates iRR with encorafenib and binimetinib (EB) and explores if adding brain radiotherapy (RDT) could improve the iPFS in pts with both asymptomatic and symptomatic BRAF mut MBM. We present final results for symptomatic pts. 15 pts were treated with 2 months of EB at standard dose. If intracranial partial response (PR) or stable disease (SD), brain RDT (radiosurgery (SRS) or whole brain RDT (WBRT) was offered according to local guidelines followed by EB. For pts with complete response (CR) RDT could be spare and used in a later progressive disease (PD). iRR, iPFS, overall survival (OS) and QoL (QLQ-C30) were analyzed. Table summarizes pts´ basal characteristics. iRR after 2 months of EB was 73.3% (6.7% CR and 66.7% PR) with 26.7% SD and no PD. 20% pts received SRS & 46.7% WBRT after 1st evaluation. With a median follow up of 11.8 months (m) (Range: 3.4-23.1) median iPFS was 9.3 m (95% CI: 7.6-NR) with 73.3 & 23.3% of pts progression free at 6 & 12m respectively. Median OS was 18.4m (95% CI: 12.1-NR) with 93.3, 72.7 & 62.3% of pts alive at 6, 12 & 18m respectively. 20% of pts experienced G3-4 toxicity from EB and 6.7% from RDT. Global health status, pain and insomnia scales improved compared to baseline at week 16 (p=0.014, 0.028 and 0.045 respectively).Table: 826PMedian age (range)49y (21-79)Sex60% femaleBrain Tumor Burden (target lesions), mean (95%CI)51.9 mm (32.9-70.9)%>ULN LDH33.3Number of target BMs (1 vs 2-3 vs >3)33.3 - 46.7 - 20Extracranial disease93.3ECOG 0-186.6Basal steroids93.3Previous systemic treatment13.3 Open table in a new tab EB achieve a significant iRR in pts with symptomatic brain BRAF mut MBM and very bad prognosis factors (need for steroids and high intracranial tumor burden). Adding brain RDT is feasible and could help to improve the intracranial disease control provided by EB.