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

Cancer Clinical Trials Unit Royal Adelaide Hospital Centre for Cancer Biology SA Pathology University of South Australia Adelaide Australia; Discipline of Medicine University of Adelaide Adelaide SA 5000 Australia

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 Fondazione Istituto di Ricerca e Cura a Carattere Scientifico Istituto Nazionale dei Tumori Milan Italy

Department of Medical Oncology Hospital Clinic Barcelona Barcelona Spain

Dermatovenerologická klinika University Hospital Prague Charles University 1st Medical Faculty Prague Czech Republic

F Hoffmann La Roche Ltd Basel Switzerland

Hospital La Paz Madrid Spain

Istituto Nazionale Tumori Fondazione Pascale Naples Italy

Istituto Oncologico Veneto Padua Italy

Klinik für Dermatologie Venerologie und Allergologie Universitätsklinikum Schleswig Holstein Campus Kiel Kiel Germany

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

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ClinicalTrials.gov
NCT01307397