Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma
Language English Country England, Great Britain Media print-electronic
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
31901705
DOI
10.1016/j.ejca.2019.11.016
PII: S0959-8049(19)30841-X
Knihovny.cz E-resources
- Keywords
- BRAF V600–mutant melanoma, BRAF inhibitor, MEK inhibitor, Overall survival,
- MeSH
- Benzimidazoles administration & dosage adverse effects MeSH
- Adult MeSH
- Outcome Assessment, Health Care methods statistics & numerical data MeSH
- Carbamates administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Melanoma drug therapy genetics pathology MeSH
- Mutation * MeSH
- Skin Neoplasms drug therapy genetics pathology MeSH
- Nausea chemically induced MeSH
- Disease-Free Survival MeSH
- Prognosis MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Proto-Oncogene Proteins B-raf genetics MeSH
- Diarrhea chemically induced MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sulfonamides administration & dosage adverse effects MeSH
- Vemurafenib administration & dosage adverse effects MeSH
- Vomiting chemically induced MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Benzimidazoles MeSH
- binimetinib MeSH Browser
- encorafenib MeSH Browser
- Carbamates MeSH
- Proto-Oncogene Proteins B-raf MeSH
- Sulfonamides MeSH
- Vemurafenib MeSH
BACKGROUND: BRAF/MEK inhibitor combinations are established treatments for BRAF V600-mutant melanoma based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). Here, we report an updated analysis of the COLUMBUS (COmbined LGX818 [encorafenib] Used with MEK162 [binimetinib] in BRAF mutant Unresectable Skin cancer) trial with long-term follow-up. METHODS: In part 1 of the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomised 1:1:1 to 450 mg of encorafenib QD + 45 mg of binimetinib BID (COMBO450) vs 960 mg of vemurafenib BID (VEM) or 300 mg of encorafenib ENCO QD (ENCO300). An updated analysis was conducted that included PFS, OS, objective response rate, safety and tolerability and analyses of results by prognostic subgroups. RESULTS: At data cutoff, there were 116, 113 and 138 deaths in the COMBO450, ENCO300 and VEM treatment arms, respectively. The median OS was 33.6 months (95% confidence interval [CI], 24.4-39.2) for COMBO450, 23.5 months (95% CI, 19.6-33.6) for ENCO300 and 16.9 months (95% CI, 14.0-24.5) for VEM. Compared with VEM, COMBO450 decreased the risk of death by 39% (hazard ratio [HR], 0.61; 95% CI, 0.48-0.79). The updated median PFS for COMBO450 was 14.9 months (95% CI, 11.0-20.2), ENCO300 was 9.6 months (95% CI, 7.4-14.8) and VEM was 7.3 months (95% CI, 5.6-7.9). PFS was longer for COMBO450 vs VEM (HR, 0.51; 95% CI, 0.39-0.67). Landmark OS and PFS results show consistent results for each year analysed. Subgroups all favoured COMBO450 vs VEM. CONCLUSIONS: Updated PFS and OS results for COMBO450 from the COLUMBUS trial demonstrate a long-term benefit in patients with advanced BRAF V600-mutated melanoma.
Cancer Center Massachusetts General Hospital Boston MA USA
Department of Dermatology National Institute of Oncology Budapest Hungary
Department of Dermatology University Hospital Tuebingen Tuebingen Germany
Department of Dermatology University Medical Center Mainz Mainz Germany
Department of Medical Oncology Hospital Clinic of Barcelona Barcelona Spain
Department of Medical Oncology Isala Zwolle Netherlands
Department of Oncology and Haematology Papa Giovanni XXIII Cancer Center Hospital Bergamo Italy
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