{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:05:04Z","timestamp":1791518704370,"version":"4.3.4"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Multidisciplinary Melanoma Group"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Encorafenib plus binimetinib (EB) is a standard-of-care treatment for advanced BRAFV600-mutant melanoma. We assessed the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>E-BRAIN\/GEM1802 was a prospective, multicenter, single-arm, phase II trial that enrolled patients with melanoma BRAFV600-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%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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\u201383.1); 10.4% complete response. Median intracranial progression-free survival (PFS) and OS were 8.5 (95% CI: 6.4\u201311.8) and 15.9 (95% CI: 10.7\u201321.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grades 3\u20134 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae116","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T08:16:24Z","timestamp":1719821784000},"page":"2074-2083","source":"Crossref","is-referenced-by-count":18,"title":["Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN\/GEM1802 phase II study)"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-668X","authenticated-orcid":false,"given":"Iv\u00e1n","family":"M\u00e1rquez-Rodas","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario Gregorio Mara\u00f1\u00f3n , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario Gregorio Mara\u00f1\u00f3n, Universidad Complutense , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Arance","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Cl\u00ednic Barcelona , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izaskun","family":"Valduvieco","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Cl\u00ednic Barcelona , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel-\u00c1ngel","family":"Berciano-Guerrero","sequence":"additional","affiliation":[{"name":"Medical Oncology Intercenter Unit, Hospitales Universitarios Regional y Virgen de la Victoria de M\u00e1laga , IBIMA-Plataforma BIONAND, M\u00e1laga ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Delgado","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario Regional de M\u00e1laga , M\u00e1laga ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainara","family":"Soria","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario Ram\u00f3n y Cajal , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fern\u00e1ndo","family":"Lopez Campos","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario Ram\u00f3n y Cajal , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario Reina Sof\u00eda , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario Reina Sof\u00eda , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Martin-Liberal","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institut Catal\u00e1 d\u2019Oncologia (ICO) L\u2019Hospitalet de Llobregat , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Institut Catal\u00e1 d\u2019Oncologia (ICO) L\u2019Hospitalet de Llobregat , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"D\u00edaz-Beveridge","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario y Polit\u00e9cnico La Fe de Valencia , Valencia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio-Jos\u00e9","family":"Conde-Moreno","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario y Polit\u00e9cnico La Fe de Valencia , Valencia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria del Carmen","family":"\u00c1lamo de la Gala","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario Virgen de la Macarena , Sevilla ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"Garc\u00eda-Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario Marqu\u00e9s de Valdecilla , Santander ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Jos\u00e9","family":"Prada","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario Marqu\u00e9s de Valdecilla , Santander ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Gonz\u00e1lez Cao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitari Dexeus, Instituto Oncol\u00f3gico Dr. Rosell , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Puertas","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario Quir\u00f3nSalud Dexeus , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Vidal","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital del Mar , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palmira","family":"Foro","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital del Mar , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Aguado de la Rosa","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Cl\u00ednico San Carlos , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Corona","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Cl\u00ednico San Carlos , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Cerezuela-Fuentes","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Cl\u00ednico Universitario (HCU) Virgen de la Arrixaca; IMIB. Ciudad de Murcia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paco","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Cl\u00ednico Universitario (HCU) Virgen de la Arrixaca; IMIB. Ciudad de Murcia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Luna","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario Son Espases , Palma de Mallorca ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neus","family":"Aymar","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario Son Espases , Palma de Mallorca ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Pu\u00e9rtolas","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario Miguel Servet , Zaragoza ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Sanagust\u00edn","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital Universitario Miguel Servet , Zaragoza ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Berrocal","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital General Universitario de Valencia , Valencia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"issue":"6","key":"2024110422223237500_CIT0001","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3322\/caac.21409","article-title":"Melanoma staging: Evidence-based changes in the American joint committee on cancer eighth edition cancer staging manual: Melanoma staging: AJCC 8 th Edition","volume":"67","author":"Gershenwald","year":"2017","journal-title":"CA Cancer J Clin."},{"key":"2024110422223237500_CIT0002","doi-asserted-by":"crossref","first-page":"9508","DOI":"10.1200\/JCO.2021.39.15_suppl.9508","article-title":"Five-year overall survival from the anti-PD1 brain collaboration (ABC Study): Randomized phase 2 study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets)","volume":"39","author":"Long","year":"2021","journal-title":"J Clin Oncol."},{"issue":"12","key":"2024110422223237500_CIT0003","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1016\/S1470-2045(21)00545-3","article-title":"Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): Final results of an open-label, multicentre, phase 2 study","volume":"22","author":"Tawbi","year":"2021","journal-title":"Lancet Oncol."},{"issue":"14","key":"2024110422223237500_CIT0004","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","article-title":"Overall survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"377","author":"Wolchok","year":"2017","journal-title":"N Engl J Med."},{"issue":"7","key":"2024110422223237500_CIT0005","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S1470-2045(17)30429-1","article-title":"Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): A multicentre, multicohort, open-label, phase 2 trial","volume":"18","author":"Davies","year":"2017","journal-title":"Lancet Oncol."},{"issue":"7","key":"2024110422223237500_CIT0006","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1056\/NEJMoa1904059","article-title":"Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma","volume":"381","author":"Robert","year":"2019","journal-title":"N Engl J Med."},{"issue":"12","key":"2024110422223237500_CIT0007","doi-asserted-by":"crossref","first-page":"e461","DOI":"10.1016\/S1470-2045(23)00334-0","article-title":"Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): A multicentre, open-label, single-arm, phase 2 study","volume":"24","author":"Dummer","year":"2023","journal-title":"Lancet Oncol."},{"issue":"36","key":"2024110422223237500_CIT0008","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.1200\/JCO.21.02659","article-title":"COLUMBUS 5-Year Update: A randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma","volume":"40","author":"Dummer","year":"2022","journal-title":"J Clin Oncol"},{"issue":"3","key":"2024110422223237500_CIT0009","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/cncr.32547","article-title":"Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series","volume":"126","author":"Holbrook","year":"2020","journal-title":"Cancer."},{"issue":"5","key":"2024110422223237500_CIT0010","doi-asserted-by":"crossref","first-page":"S870","DOI":"10.1016\/j.annonc.2021.08.1423","article-title":"1038MO Intracranial activity of encorafenib and binimetinib followed by radiotherapy in patients with BRAF mutated melanoma and brain metastasis: Preliminary results of the GEM1802\/EBRAIN-MEL phase II clinical trial","volume":"32","author":"Marquez-Rodas","year":"2021","journal-title":"Ann Oncol."},{"key":"2024110422223237500_CIT0011","doi-asserted-by":"crossref","first-page":"9501","DOI":"10.1200\/JCO.2019.37.15_suppl.9501","article-title":"Efficacy and safety of the combination of nivolumab (NIVO) plus ipilimumab (IPI) in patients with symptomatic melanoma brain metastases (CheckMate 204)","volume":"37","author":"Tawbi","year":"2019","journal-title":"J Clin Oncol."},{"issue":"11","key":"2024110422223237500_CIT0012","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/j.annonc.2020.07.004","article-title":"ESMO consensus conference recommendations on the management of metastatic melanoma: Under the auspices of the ESMO guidelines committee","volume":"31","author":"Keilholz","year":"2020","journal-title":"Ann Oncol"},{"issue":"6","key":"2024110422223237500_CIT0013","doi-asserted-by":"crossref","first-page":"e270","DOI":"10.1016\/S1470-2045(15)70057-4","article-title":"Response assessment criteria for brain metastases: Proposal from the RANO group","volume":"16","author":"Lin","year":"2015","journal-title":"Lancet Oncol."}],"container-title":["Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/advance-article-pdf\/doi\/10.1093\/neuonc\/noae116\/58576125\/noae116.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article-pdf\/26\/11\/2074\/60416255\/noae116.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article-pdf\/26\/11\/2074\/60416255\/noae116.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T22:22:49Z","timestamp":1730758969000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/article\/26\/11\/2074\/7702016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":13,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,7,1]]},"published-print":{"date-parts":[[2024,11,4]]}},"URL":"https:\/\/doi.org\/10.1093\/neuonc\/noae116","relation":{},"ISSN":["1522-8517","1523-5866"],"issn-type":[{"value":"1522-8517","type":"print"},{"value":"1523-5866","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,11]]},"published":{"date-parts":[[2024,7,1]]}}}