Publication date: Nov 30, 2019
Purpose To validate a plasma vemurafenib steady-state trough concentration (C,) threshold that predicts survival outcomes of patients with BrafV mutated melanoma.
A pooled analysis of individual patient data from two advanced melanoma trials involving vemurafenib?+/-?cobimetinib therapy was performed. Day 23 was chosen as the landmark time when steady-state concentration reached. Optimal C, threshold was determined via assessment of discriminative performance and model fitting. Association between vemurafenib C, and survival was modelled using Cox proportional hazards regression.
Vemurafenib plasma concentration data were available for 402 patients who were on stable dose for the first 3 weeks. When compared to a previously described plasma vemurafenib C, threshold of 42 mg/L, we identified that a cutoff concentration of 50 mg/L by day 23 was strongly associated with progression-free survival and overall survival. The association remained statistically significant after adjusting for important clinical confounding variables. Sub-group analysis showed that while the addition of cobimetinib resulted in a lower day 23 plasma vemurafenib C,, the threshold was still associated with overall survival and not in the monotherapy cohort.
A plasma vemurafenib C, threshold of 50 mg/L is strongly associated with survival outcomes in patients with advanced melanoma. This new threshold needs to be validated prospectively in future studies.
Kichenadasse, G., Hughes, J.H., Miners, J.O., Mangoni, A.A., Rowland, A., Hopkins, A.M., and Sorich, M.J. Relationship between vemurafenib plasma concentrations and survival outcomes in patients with advanced melanoma. 24991. 2019 Cancer Chemother Pharmacol.
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