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Multicenter Study
. 2019 Jan:107:175-185.
doi: 10.1016/j.ejca.2018.11.018. Epub 2018 Dec 20.

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

James Larkin  1 , Michael P Brown  2 , Ana M Arance  3 , Axel Hauschild  4 , Paola Queirolo  5 , Michele Del Vecchio  6 , Paolo A Ascierto  7 , Ivana Krajsová  8 , Jacob Schachter  9 , Bart Neyns  10 , Claus Garbe  11 , Vanna Chiarion Sileni  12 , Mario Mandalà  13 , Helen Gogas  14 , Enrique Espinosa  15 , Geke Hospers  16 , Paul Lorigan  17 , Marta Nyakas  18 , Alex Guminski  19 , Gabriela Liszkay  20 , Piotr Rutkowski  21 , Wilson Miller Jr  22 , Margarita Donica  23 , Martina Makrutzki  23 , Christian Blank  24
Affiliations
Multicenter Study

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

James Larkin et al. Eur J Cancer. 2019 Jan.

Abstract

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.

Keywords: BRAF(V600) mutation; Metastatic melanoma; Prognostic scoring system; Safety; Vemurafenib.

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