Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management
Language English Country Great Britain, England Media print-electronic
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
31437754
DOI
10.1016/j.ejca.2019.07.016
PII: S0959-8049(19)30424-1
Knihovny.cz E-resources
- Keywords
- Binimetinib, Encorafenib, Melanoma, Safety, Vemurafenib,
- MeSH
- Benzimidazoles administration & dosage adverse effects MeSH
- Incidence MeSH
- Protein Kinase Inhibitors administration & dosage adverse effects therapeutic use MeSH
- Carbamates administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Melanoma drug therapy genetics metabolism MeSH
- Mitogen-Activated Protein Kinases antagonists & inhibitors metabolism MeSH
- Mutation MeSH
- Skin Neoplasms drug therapy genetics metabolism MeSH
- Nausea chemically induced epidemiology MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects therapeutic use MeSH
- Proto-Oncogene Proteins B-raf antagonists & inhibitors genetics metabolism MeSH
- Sulfonamides administration & dosage adverse effects MeSH
- Fatigue chemically induced epidemiology MeSH
- Vemurafenib administration & dosage adverse effects MeSH
- Vomiting chemically induced epidemiology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male 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
- Protein Kinase Inhibitors MeSH
- Carbamates MeSH
- Mitogen-Activated Protein Kinases MeSH
- Proto-Oncogene Proteins B-raf MeSH
- Sulfonamides MeSH
- Vemurafenib MeSH
BACKGROUND: Dual inhibition of the mitogen-activated protein kinase pathway with BRAF/MEK inhibitor (BRAFi/MEKi) therapy is a standard treatment for BRAFV600-mutant metastatic melanoma and has historically been associated with grade III pyrexia or photosensitivity depending on the combination used. The objective of this study was to fully describe adverse events from the COLUMBUS study evaluating the most recent BRAF/MEK inhibitor combination encorafenib+binimetinib. PATIENTS AND METHODS: Patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma were randomised to receive encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, encorafenib 300 mg once daily or vemurafenib 960 mg twice daily. Adverse events that represent known effects of available BRAFi and/or MEKi were evaluated. RESULTS: The safety population included a total of 570 patients (encorafenib+binimetinib = 192; encorafenib = 192; vemurafenib = 186). Median duration of exposure was longer with encorafenib+binimetinib (51 weeks) than with encorafenib (31 weeks) or vemurafenib (27 weeks). Common BRAFi/MEKi toxicities with encorafenib+binimetinib were generally manageable, reversible and infrequently associated with discontinuation. Pyrexia was less frequent with encorafenib+binimetinib (18%) and encorafenib (16%) than with vemurafenib (30%) and occurred later in the course of therapy with encorafenib+binimetinib (median time to first onset: 85 days versus 2.5 days and 19 days, respectively). The incidence of photosensitivity was lower with encorafenib+binimetinib (5%) and encorafenib (4%) than with vemurafenib (30%). The incidence of serous retinopathy was higher with encorafenib+binimetinib (20%) than with encorafenib (2%) or vemurafenib (2%), but no patients discontinued encorafenib+binimetinib because of this event. CONCLUSION: Encorafenib+binimetinib is generally well tolerated and has a low discontinuation rate in patients with BRAFV600-mutant melanoma, with a distinct safety profile as compared with other anti-BRAF/MEK targeted therapies. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01909453) and with EudraCT (number 2013-001176-38).
Array BioPharma Inc Boulder CO USA
Cancer Center Massachusetts General Hospital Boston MA USA
Department of Dermatologic Oncology National Cancer Center Hospital Tokyo Japan
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
Melanoma Cancer Unit Oncology Institute of Veneto IRCCS Padua Italy
References provided by Crossref.org
ClinicalTrials.gov
NCT01909453
