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An open-label, multicentre safety study of vemurafenib in patients with BRAFV600-mutant metastatic melanoma: final analysis and a validated prognostic scoring system
J. Larkin, MP. Brown, AM. Arance, A. Hauschild, P. Queirolo, MD. Vecchio, PA. Ascierto, I. Krajsová, J. Schachter, B. Neyns, C. Garbe, VC. Sileni, M. Mandalà, H. Gogas, E. Espinosa, G. Hospers, P. Lorigan, M. Nyakas, A. Guminski, G. Liszkay, P....
Language English Country Great Britain
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
- MeSH
- Humans MeSH
- Lymphatic Metastasis MeSH
- Melanoma drug therapy genetics pathology MeSH
- Survival Rate MeSH
- Mutation * MeSH
- Brain Neoplasms drug therapy genetics secondary MeSH
- Follow-Up Studies MeSH
- Nomograms * MeSH
- Prognosis MeSH
- Antineoplastic Agents therapeutic use MeSH
- Proto-Oncogene Proteins B-raf genetics MeSH
- Aged MeSH
- Validation Studies as Topic MeSH
- Vemurafenib therapeutic use MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAFV600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population. PATIENTS AND METHODS: In this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAFV600 mutation received vemurafenib 960 mg twice daily. The primary endpoint was safety. In a post hoc analysis, overall survival (OS) was analysed according to a prognostic scoring system developed using Eastern Cooperative Oncology Group performance status, existence of brain metastases and baseline serum lactate dehydrogenase level. The index was validated using data from patients treated with vemurafenib or dacarbazine in three clinical trials and data from patients treated with vemurafenib plus cobimetinib in two studies. The study is registered with ClinicalTrials.gov (NCT01307397). RESULTS: Between March 2011 and January 2013, 3224 patients were enrolled, and 3219 patients received ≥1 dose of vemurafenib (safety population); median follow-up time was 33.4 months. Vemurafenib's long-term benefits were confirmed, and no new safety signals identified. The prognostic index showed between-group differences in OS, with tight, non-overlapping confidence intervals. Validation in a pooled group of 666 vemurafenib-treated clinical trial patients revealed a similar pattern; the pattern was similar in 280 patients treated with vemurafenib plus cobimetinib. CONCLUSIONS: Final results from the vemurafenib safety study confirm vemurafenib's tolerability in BRAFV600 mutation-positive patients and resemble those seen in real-world clinical practice. This index may be useful in patients on combination therapy and as a basis for further work.
Afdelingshoofd Medische Oncologie Brussels Belgium
Chaim Sheba Medical Centre Oncology Institute Ramat Gan Israel
Christie NHS Foundation Trust Manchester UK
Department of Dermatology University Medical Center Tuebingen Germany
Department of Dermatooncology National Institute of Oncology Budapest Hungary
Department of Medical Oncology Hospital Clinic Barcelona Barcelona Spain
Discipline of Medicine University of Adelaide Adelaide SA 5000 Australia
F Hoffmann La Roche Ltd Basel Switzerland
Istituto Nazionale Tumori Fondazione Pascale Naples Italy
Istituto Oncologico Veneto Padua Italy
Maria Sklodowska Curie Memorial Cancer Center Institute of Oncology Warsaw Poland
McGill University Segal Cancer Centre Montreal Quebec Canada
Melanoma Institute Australia Royal North Shore Hospital University of Sydney Sydney Australia
Oslo University Hospital Oslo Norway
Papa Giovanni XXIII Hospital Bergamo Italy
The Netherlands Cancer Institute Amsterdam the Netherlands
The Royal Marsden NHS Foundation Trust London UK
University Medical Centre Groningen Groningen the Netherlands
University of Athens Athens Greece
UOC Oncologia Medica Istituto di Ricerca e Cura a Carattere Scientifico San Martino IST Genova Italy
References provided by Crossref.org
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