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Encorafenib and binimetinib followed by radiotherapy for patients with BRAF<SUP>V600</SUP>-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study)

dc.contributor.authorMarquez-Rodas, Ivan
dc.contributor.authorAlvarez, Ana
dc.contributor.authorArance, Ana
dc.contributor.authorValduvieco, Izaskun
dc.contributor.authorBerciano-Guerrero, Miguel-angel
dc.contributor.authorDelgado, Raquel
dc.contributor.authorSoria, Ainara
dc.contributor.authorLopez-Campos, Fernando
dc.contributor.authorSanchez, Pedro
dc.contributor.authorRomero, Jose Luis
dc.contributor.authorMartin-Liberal, Juan
dc.contributor.authorLucas, Anna
dc.contributor.authorDiaz-Beveridge, Roberto
dc.contributor.authorConde-Moreno, Antonio-Jose
dc.contributor.authorAlamo-de-la-Gala, Maria del Carmen
dc.contributor.authorGarcia-Castano, Almudena
dc.contributor.authorPrada, Pedro Jose
dc.contributor.authorGonzalez-Cao, Maria
dc.contributor.authorPuertas, Enrique
dc.contributor.authorVidal, Joana
dc.contributor.authorForo, Palmira
dc.contributor.authorAguado-de-la-Rosa, Carlos
dc.contributor.authorCorona, Juan Antonio
dc.contributor.authorCerezuela-Fuentes, Pablo
dc.contributor.authorLopez, Paco
dc.contributor.authorLuna, Pablo
dc.contributor.authorAymar, Neus
dc.contributor.authorPuertolas, Teresa
dc.contributor.authorSanagustin, Pilar
dc.contributor.authorBerrocal, Alfonso
dc.contributor.funderSpanish Multidisciplinary Melanoma Group (GEM)
dc.date.accessioned2025-05-28T17:59:17Z
dc.date.available2025-05-28T17:59:17Z
dc.date.issued2024-07-01
dc.description.abstractBackground. 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.
dc.description.versionYes
dc.identifier.citationMárquez-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
dc.identifier.doi10.1093/neuonc/noae116
dc.identifier.issn1522-8517
dc.identifier.urihttps://hdl.handle.net/10668/28507
dc.identifier.wosIDWOS:001270732200001
dc.issue.number11
dc.journal.titleNeuro-Oncology
dc.language.isoen
dc.page.number10
dc.publisherOxford University Press
dc.relation.publisherversionhttps://academic.oup.com/neuro-oncology/article-lookup/doi/10.1093/neuonc/noae116
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBrain metastasis
dc.subjectEncorafenib and binimetinib
dc.subjectMelanoma
dc.subjectRadiotherapy
dc.subjectTargeted therapy
dc.subject.decsRadioterapia
dc.subject.decsEncéfalo
dc.subject.decsSupervivencia sin progresión
dc.subject.decsInutilidad médica
dc.subject.decsMetástasis de la neoplasia
dc.subject.decsCorticoesteroides
dc.subject.meshProto-Oncogene Proteins B-raf
dc.subject.meshAlanine Transaminase
dc.subject.meshProgression-Free Survival
dc.subject.meshMedical Futility
dc.subject.meshBrain Neoplasms
dc.subject.meshSteroids
dc.subject.meshAdrenal Cortex Hormones
dc.titleEncorafenib and binimetinib followed by radiotherapy for patients with BRAF<SUP>V600</SUP>-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study)
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number26
dspace.entity.typePublication

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