Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma
Year: 2024
Type: article
Study design: Observational Study
Abstract: BACKGROUND: In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI. PATIENTS AND METHODS: This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of disease, and received dabrafenib/trametinib (dab/tram) as 2L adjuvant therapy. The primary endpoint was relapse-free survival (RFS) from initiation of 2L adjuvant dab/tram (RFS-2), analyzed via Kaplan-Meier methods. RESULTS: Thirty-eight patients were included (median age 50 years, 63% male, 87% stage III, median follow-up 19 months from 2L dab/tram initiation). Median dab/tram duration was 10.1 months (range: 1 day-22.7 months), with half discontinuing due to progression or adverse events. Median (95% CI) RFS-2 was 18.9 (14.9-28.1) months, with 91%, 81%, and 58% remaining relapse-free at 6, 12, and 18 months, respectively. Most patients remained distant metastasis-free at 6, 12, and 18 months (97%, 85%, and 71%, respectively). Two patients were deceased at the last follow-up, with 97% alive at 18 months. CONCLUSIONS: Over 80% of patients remained relapse- and metastasis-free at 12 months after 2L dab/tram initiation, with only 2 deaths observed. Dab/tram appears to have activity in the 2L adjuvant setting, although more follow-up is required.
Source: The Oncologist
Authors: Jeffrey Weber, Waqas Haque, Svetomir N Markovic, April K S Salama, Inderjit Mehmi, Ryan J Sullivan, Yana G Najjar, Alexander C J van Akkooi, Alexander M Menzies, Georgina V Long, Amelia M Taylor, John Haanen, Lisanne P Zijlker, Keith L Davis, Siddharth Karanth, Deborah Norton, Lucy Connolly
Institutions: NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, Mayo Clinic, Mayo Clinic Comprehensive Cancer Center (Minnesota), Duke University, Duke Medical Center, Angeles Clinic and Research Institute, Massachusetts General Hospital, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, The University of Sydney, The Netherlands Cancer Institute, Melanoma Institute Australia, Royal North Shore Hospital, Centre Hospitalier Universitaire Vaudois, RTI Health Solutions, Novartis (Ireland)
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,045
Funders: Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, Hexal AG, Array BioPharma, Novartis Pharmaceuticals Corporation, Moffitt Cancer Center, Regeneron Pharmaceuticals, Les Laboratories Pierre Fabre, BeiGene, Incyte, Innovent Biologics, Moderna, Seagen, Eisai, Ipsen, Melanoma Institute Australia, Qbiotics, NeraCare, Genentech, National Health and Medical Research Council
OpenAlex ID: W4404495784