{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:59:10Z","timestamp":1788479950076,"version":"build-2803163510"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Lessons Learned<\/jats:title>\n                  <jats:p>This study suggests that trametinib has significant clinical activity in non-V600 BRAF mutation and BRAF fusion metastatic melanoma, albeit in a small cohort. All patients with metastatic melanoma should undergo sequencing of the BRAF gene to identify noncanonical BRAF mutations that may indicate benefit from treatment with trametinib.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Non-V600 BRAF mutations and BRAF fusions in aggregate occur in approximately 5% of all melanomas. Inhibition of the mitogen-activated protein kinase (MAPK) pathway has been implicated as a possible treatment strategy for these patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this open-label, multicenter, phase II study, patients with advanced melanoma harboring mutations in BRAF outside V600 (non-V600) or BRAF fusions received trametinib 2.0 mg daily. Patients were divided into cohorts based on the intrinsic catalytic activity of BRAF mutation (high, cohort A; low\/unknown, cohort B). The primary endpoint was objective response rate (ORR) for patients in cohort A; secondary endpoints included ORR in cohort B, safety, and survival in both treatment arms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among all patients, the ORR was 33% (three of nine patients), including 67% in cohort A and 17% in cohort B. Two patients had stable disease as best response, and six patients had some degree of tumor shrinkage. The median progression-free survival (PFS) was 7.3 months. Treatment-related adverse events occurred in all patients (100%); most (89%) were grade 1\u20132.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In contrast to recently described tumor-agnostic studies in a genetically similar population, trametinib had considerable activity in a small population of patients with melanoma harboring BRAF non-V600 mutations and fusions, providing rationale for sequencing in search of these genomic alterations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/onco.13795","type":"journal-article","created":{"date-parts":[[2021,4,17]],"date-time":"2021-04-17T00:37:56Z","timestamp":1618619876000},"page":"731-e1498","source":"Crossref","is-referenced-by-count":43,"title":["Efficacy and Safety of Trametinib in <scp>Non-V600 <i>BRAF<\/i>\n                  <\/scp> Mutant Melanoma: A Phase II Study"],"prefix":"10.1093","volume":"26","author":[{"given":"Caroline A.","family":"Nebhan","sequence":"first","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roda N.","family":"Amaria","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Oncology, MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith T.","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Sosman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Robert H. 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