BACKGROUND: Treatment with encorafenib plus binimetinib and encorafenib monotherapy is associated with improved progression-free survival (PFS) and overall survival (OS) compared with vemurafenib in patients with BRAF V600E/K-mutant metastatic melanoma. We report results from the 7-year analysis of COLUMBUS part 1 (NCT01909453) at 99.7 months (median duration between randomization and data cutoff). METHODS: 577 patients with locally advanced unresectable or metastatic BRAF V600E/K-mutant melanoma who were treatment-naive or progressed after first-line immunotherapy were randomized 1:1:1 to encorafenib 450 mg once daily (QD) plus binimetinib 45 mg twice daily (BID) (n = 192), vemurafenib 960 mg BID (n = 191), or encorafenib monotherapy 300 mg QD (n = 194). No prior BRAF/MEK inhibitor was allowed. RESULTS: Seven-year PFS and OS rates (95 % CI) were 21.2 % (14.7-28.4 %) and 27.4 % (21.2-33.9%) in the encorafenib plus binimetinib arm and 6.4 % (2.1-14.0 %) and 18.2 % (12.8-24.3 %) in the vemurafenib arm, respectively. Median melanoma-specific survival (95 % CI) was 36.8 months (27.7-51.5 months) in the encorafenib plus binimetinib arm and 19.3 months (14.8-25.9 months) in the vemurafenib arm. Thirty-four long-term responders (complete/partial response ongoing at 7 years) were identified across arms. CONCLUSIONS: This is the longest follow-up from a phase III trial of BRAF/MEK inhibitor combination in BRAF V600E/K-mutant metastatic melanoma. Safety results were consistent with the known tolerability profile of encorafenib plus binimetinib. Results support the long-term efficacy and known safety of encorafenib plus binimetinib in this population and provide new insights on long-term responders. Interactive data visualization is available at the COLUMBUS dashboard (https://clinical-trials.dimensions.ai/columbus7/).

Gustave Roussy and Paris Saclay University Villejuif France

Hannover Medical School Hannover and Ruhr University Bochum Minden Campus Germany

Hospital Clinic of Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain

Isala Oncology Center Zwolle the Netherlands

Massachusetts General Hospital Cancer Center Boston MA USA

Melanoma and Sarcoma Division IEO European Institute of Oncology IRCCS Milan Italy

Melanoma Cancer Immunotherapy and Innovative Therapies Unit Istituto Nazionale Tumori IRCCS Fondazione Pascale Napoli Italy

National and Kapodistrian University of Athens Athens Greece

National Cancer Center Hospital Tokyo Japan

National Institute of Oncology Budapest Hungary

Pfizer Milan Italy

Pfizer New York NY USA

Pfizer Sandwich UK

University Hospital Essen West German Cancer Center and German Cancer Consortium Partner Site Essen Essen Germany; National Center for Tumor Diseases West Campus Essen and Research Alliance Ruhr Research Center One Health University of Duisburg Essen Essen Germany

University Hospital Prague Prague Czech Republic

University Hospital Tübingen Tübingen Germany

University Hospital Zurich Zurich Switzerland

University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany

University of Perugia Perugia Italy

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