An open-label, multicentre safety study of vemurafenib in patients with BRAFV600-mutant metastatic melanoma: final analysis and a validated prognostic scoring system. (January 2019)

• Record Type: Journal Article
• Authors: Larkin, James; Brown, Michael P.; Arance, Ana M.; Hauschild, Axel; Queirolo, Paola; Vecchio, Michele Del; Ascierto, Paolo A.; Krajsová, Ivana; Schachter, Jacob; Neyns, Bart; Garbe, Claus; Sileni, Vanna Chiarion; Mandalà, Mario; Gogas, Helen; Espinosa, Enrique; Hospers, Geke; Lorigan, Paul; Nyakas, Marta; Guminski, Alex; Liszkay, Gabriela; Rutkowski, Piotr; Miller, Wilson; Donica, Margarita; Makrutzki, Martina; Blank, Christian
• Is Part Of: European journal of cancer. Volume 107(2019)
• Page Start: 175
• Page End: 185
• Publication Date: 2019-01
• Subjects: BRAFV600 mutation -- Metastatic melanoma -- Vemurafenib -- Safety -- Prognostic scoring system; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.11.018
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAF V600 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 BRAF V600 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 withClinicalTrials.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 BRAF V600 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. Highlights: Vemurafenib was generally tolerable in patients with metastatic melanoma. We developed a prognostic index that allowed estimation of overall survival. The prognostic index showed survival differences, with tight, non-overlapping confidence intervals. Validation in vemurafenib-treated clinical trial patients revealed a similar pattern. This prognostic index may be useful as a basis for further studies.