Vemurafenib for BRAF V600 mutated advanced melanoma: Results of treatment beyond progression

Background:Selective BRAF inhibition (BRAFi) by vemurafenib or dabrafenib has become approved standard treatment in BRAF V600 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. Our observation of accelerated disease progression within some patients after stopping vemurafenib treatment has fostered the idea of treatment beyond progression (BRAFi TBP). Method In this retrospective study, we analysed 70 metastatic melanoma patients, treated at our institute, who experienced progression after prior objective response upon treatment with vemurafenib. Thirty-five 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% confidence interval (CI): 3.8-7.4 versus 0.6-3.4; Log-Rank p = 0.002) in favour of BRAFi TBP. In the multivariate survival analysis, stopping treatment at disease progression was significantly associated with shorter survival (hazard ratio: 1.92; 95% CI: 1.04-3.55; p = 0.04). Conclusion Our results suggest that continuing vemurafenib treatment beyond progression may be beneficial in advanced melanoma patients, who prior to progression responded to vemurafenib.