Vemurafenib improved survival in patients with BRAF-mutant metastatic melanoma in phase III trials. We examined the survival of vemurafenib in real-world clinical practice in the Netherlands and factors associated with survival.
Data of all metastatic melanoma patients in The Netherlands who at least received one dose of vemurafenib between July 1st 2012 and March 29th 2016 were retrieved from the Dutch Melanoma Treatment Registry (follow-up data cut-off March 29th 2016). We assessed overall median survival (OS) using Kaplan-Meier estimates. A multivariable cox regression analysis was used to identify factors associated with survival.
A total of 662 patients (treatment naïve or previously treated) with BRAF-mutant metastatic melanoma received at least one dose of vemurafenib. Median follow-up was 27.8 months (95% CI 25.5-30.1). Median OS was 7.3 months (95%CI 6.6-8.0). Subgroup analysis showed a median OS of 4.0 months (95% CI 3.5-4.5) for patients with a WHO performance score ≥2 (n = 124), 6.3 months (95%CI 5.6-6.9), for patients with M1c stage (n = 546), 4.9 months (95%CI 4.4-5.4) for patients with elevated serum LDH levels (n = 280) and 5.4 months (95% CI 4.3-6.4) for patients with symptomatic brain metastases (n = 122). A subset of patients with a combination of more favorable features (WHO score 0-1 and normal LDH levels without brain metastases; n = 118) had a median OS of 9.8 months (95%CI 7.9 – 11.6). Multivariable cox regression showed that a lower disease stage and normal LDH levels were the strongest predictors for a higher survival.
Real-world median overall survival in The Netherlands of patients treated with vemurafenib appears to be somewhat lower than reported in earlier trials. However, in our cohort more patients with poor prognostic factors were registered and patients were included with brain metastases and WHO ≥ 2, both exclusion criteria from earlier trials. We have demonstrated that subgroups with more favorable baseline factors have a higher survival. This knowledge can be used to further characterize baseline characteristics as prognostic markers for selecting BRAF-mutant metastatic patients who may benefit most from vemurafenib.
Clinical trial identification
Not applicable to this study becayse data is derived from a quality registry.
Legal entity responsible for the study
Dutch Society of Medical Oncologists (NVMO)
The DMTR is funded by a grant form the Netherlands Organization for Health Research and Development (ZonMw) (no.836002002). The DMTR is financially established with sponsoring of Roche Nederland B.V, Bristol- Myers Squibb (BMS), GlaxoSmithKline (GSK)/ Novartis and Merck Sharp & Dohme (MSD).
A. van den Eertwegh: reports serving on advisory boards of Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Applied Molecular Genetics Inc. and Roche. G. Groenewegen: reports participation in a speakers' bureau of Astellas. J-W. de Groot: reports serving on advisory boards of BMS, Roche, Celgene, Merck, Bayer and Amgen. J.B.A.G. Haanen: is on advisory boards of Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche, Pfizer, and NEON therapeutics and has received research funding from Bristol-Myers Squibb, Merck Sharp & Dohme, and Glaxo Smith Kline. R. Koornstra: reports serving on advisory boards of BMS, Roche, MSD and Novartis. W. Kruit: reports serving on advisory boards of BMS, Novartis and GSK. D. Piersma: reports serving on advisory boards of Novartis and Amgen and received research funding from Novartis, BMS and AstraZeneca. R. van Rijn: reports serving on advisory boards of BMS, Amgen and Takeda and received research funding from GSK and Celgene. G. Vreugdenhil: reports serving on advisory boards of BMS. M. Wouters: received research funding from Novartis. All other authors have declared no conflicts of interest.