Vemurafenib for Braf V600 Mutated Advanced Melanoma: Results of Treatment Beyond Progression

Abstract

ABSTRACT Aim: Background Selective BRAF inhibition (BRAFi) by vemurafenib or dabrafenib has become approved standard treatment in BRAFV600 mutated advanced stage melanoma. While the response rate is high, the response duration is limited with a progression-free survival (PFS) of 5-6 months months. Our observation of accelerated disease progression within some patients after stopping vemurafenib treatment has fostered the idea of treatment beyond progression (TBP). Methods: In this retrospective study, we analyzed 70 metastatic melanoma patients, treated at our institute, who experienced progression after prior objective response upon treatment with vemurafenib. Thirtyfive patients that continued treatment beyond progression are compared with 35 patients who stopped BRAFi treatment at disease progression. Results: Median overall survival beyond documented progression was found to be 5.2 months versus 1.4 months (95% CI: 3.8-7.4 vs. 0.6-3.4; Log-Rank p = 0.0001) in favour of TBP. In the multivariate survival analysis, stopping treatment at disease progression was independently and significantly associated with shorter survival (Hazard Ratio: 1.92; 95% CI: 1.04-3.55; p = 0.04). Conclusions: Our results clearly suggest that continuing vemurafenib treatment beyond progression may be beneficial in advanced melanoma patients. Prospective confirmation, however, is warranted before implementation into daily practice. Disclosure: J.B.A.G. Haanen: Advisory role and research grant form GSK. All other authors have declared no conflicts of interest.