{"doi":"10.1002/onco.13795","title":"Efficacy and Safety of Trametinib in <scp>Non-V600 <i>BRAF</i> </scp> Mutant Melanoma: A Phase II Study","abstract":"LESSONS LEARNED: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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 1-2. CONCLUSION: 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.","journal":"The Oncologist","year":2021,"id":163082,"datarank":1.494894007139649,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.9272655620519098,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.9272655620519098,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":34,"citers_with_citation_signal":28,"citers_with_endowment":28,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":28327,"name":"Douglas B. Johnson","orcid":"0000-0002-6390-773X","position":1,"is_corresponding":false},{"id":412,"name":"Ryan J. Sullivan","orcid":"0000-0001-5344-6645","position":2,"is_corresponding":false},{"id":682716,"name":"R. Amaria","orcid":null,"position":3,"is_corresponding":false},{"id":410,"name":"Keith T. Flaherty","orcid":"0000-0002-3402-0478","position":4,"is_corresponding":false},{"id":232507,"name":"Jeffrey A. Sosman","orcid":"0000-0002-0650-9698","position":5,"is_corresponding":false},{"id":72141,"name":"Michael A. Davies","orcid":"0000-0002-0977-0912","position":6,"is_corresponding":false},{"id":332265,"name":"Caroline A. Nebhan","orcid":"0000-0002-9402-7284","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:45:17.971865Z","pmid":"33861486","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}