RT Journal Article T1 Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study) A1 Marquez-Rodas, Ivan A1 Alvarez, Ana A1 Arance, Ana A1 Valduvieco, Izaskun A1 Berciano-Guerrero, Miguel-angel A1 Delgado, Raquel A1 Soria, Ainara A1 Lopez-Campos, Fernando A1 Sanchez, Pedro A1 Romero, Jose Luis A1 Martin-Liberal, Juan A1 Lucas, Anna A1 Diaz-Beveridge, Roberto A1 Conde-Moreno, Antonio-Jose A1 Alamo-de-la-Gala, Maria del Carmen A1 Garcia-Castano, Almudena A1 Prada, Pedro Jose A1 Gonzalez-Cao, Maria A1 Puertas, Enrique A1 Vidal, Joana A1 Foro, Palmira A1 Aguado-de-la-Rosa, Carlos A1 Corona, Juan Antonio A1 Cerezuela-Fuentes, Pablo A1 Lopez, Paco A1 Luna, Pablo A1 Aymar, Neus A1 Puertolas, Teresa A1 Sanagustin, Pilar A1 Berrocal, Alfonso K1 Brain metastasis K1 Encorafenib and binimetinib K1 Melanoma K1 Radiotherapy K1 Targeted therapy AB Background. Encorafenib plus binimetinib (EB) is a standard-of-care treatment for advanced BRAF(V600)-mutant melanoma. We assessed the efficacy and safety of encorafenib plus binimetinib in patients with BRAF(V600)-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. Methods. E-BRAIN/GEM1802 was a prospective, multicenter, single-arm, phase II trial that enrolled patients with melanoma BRAF(V600)-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved a partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression. Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. Results. The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After 2 months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial progression-free survival (PFS) and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grades 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). Conclusions. Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high-grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response. PB Oxford University Press SN 1522-8517 YR 2024 FD 2024-07-01 LK https://hdl.handle.net/10668/28507 UL https://hdl.handle.net/10668/28507 LA en NO Márquez-Rodas I, Álvarez A, Arance A, Valduvieco I, Berciano-Guerrero MÁ, Delgado R, et al. Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study). Neuro Oncol. 2024 Nov 4;26(11):2074-2083 DS RISalud RD Sep 25, 2025