{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:05:06Z","timestamp":1791518706850,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T00:00:00Z","timestamp":1572220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007174","name":"Array BioPharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007174","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sixty percent of patients with stage IV melanoma may develop brain metastases, which result in significantly increased morbidity and a poor overall prognosis. Phase 3 studies of melanoma usually exclude patients with untreated brain metastases; therefore, clinical data for intracranial responses to treatments are limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A multicenter, retrospective case series investigation of consecutive <jats:italic>BRAF<\/jats:italic>\u2010mutant patients with melanoma brain metastases (MBMs) treated with a combination of BRAF inhibitor encorafenib and MEK inhibitor binimetinib was conducted to evaluate the antitumor response. Assessments included the intracranial, extracranial, and global objective response rates (according to the modified Response Evaluation Criteria in Solid Tumors, version 1.1); the clinical benefit rate; the time to response; the duration of response; and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 24 patients with stage IV <jats:italic>BRAF<\/jats:italic>\u2010mutant MBMs treated with encorafenib plus binimetinib in 3 centers in the United States were included. Patients had received a median of 2.5 prior lines of treatment, and 88% had prior treatment with BRAF\/MEK inhibitors. The intracranial objective response rate was 33%, and the clinical benefit rate was 63%. The median time to a response was 6\u00a0weeks, and the median duration of response was 22\u00a0weeks. Among the 21 patients with MBMs and prior BRAF\/MEK inhibitor treatment, the intracranial objective response rate was 24%, and the clinical benefit rate was 57%. Similar outcomes were observed for extracranial and global responses. The safety profile for encorafenib plus binimetinib was similar to that observed in patients with melanoma without brain metastases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Combination therapy with encorafenib plus binimetinib elicited intracranial activity in patients with <jats:italic>BRAF<\/jats:italic>\u2010mutant MBMs, including patients previously treated with BRAF\/MEK inhibitors. Further prospective studies are warranted and ongoing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.32547","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T12:42:49Z","timestamp":1572266569000},"page":"523-530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series"],"prefix":"10.1002","volume":"126","author":[{"given":"Kourtney","family":"Holbrook","sequence":"first","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Lutzky","sequence":"additional","affiliation":[{"name":"Mount Sinai Comprehensive Cancer Center Miami Beach Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Davies","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Michaud","family":"Davis","sequence":"additional","affiliation":[{"name":"Levine Cancer Institute, Atrium Health Charlotte North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella C.","family":"Glitza","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodabe N.","family":"Amaria","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Diab","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1339-1517","authenticated-orcid":false,"given":"Sapna P.","family":"Patel","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim","family":"Amin","sequence":"additional","affiliation":[{"name":"Levine Cancer Institute, Atrium Health Charlotte North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Tawbi","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12538"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1998.88.1.0011"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21254"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/EdBook_AM.2013.33.393"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2964(78)90201-3"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25634"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-013-1160-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70431-X"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60398-5"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.11.002"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000527"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805453"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.1206"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30429-1"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26724"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-016-0879-9"},{"key":"e_1_2_8_18_1","unstructured":"Center for Drug Evaluation and Research.Approved drugs\u2013trametinib and dabrafenib. 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