Impact of trough concentrations of regorafenib and its major metabolites M-2 and M-5 on overall survival of chemorefractory metastatic colorectal cancer patients: Results from a multicentre GERCOR TEXCAN phase II study

Abstract

Purpose: This prospective pharmacokinetic (PK) ancillary study of the TEXCAN phase II GERCOR trial of patients with chemorefractory metastatic colorectal cancer and treated with regorafenib (REGO) investigated correlations between overall survival (OS) and concentrations (C) of REGO and its active metabolites, M-2 and M-5. Methods: 55 patients received REGO 160 mg/day for 21 days of a 28-day cycle (NCT02699073). REGO, M-2, M-5 were measured by liquid chromatography-mass spectrometry assay on day 15 of cycle 1 (C1) and 2 (C2). We studied the association between OS and Cmin of REGO, M-2 and M-5 at C1 and their accumulations between C1 and C2. Results: Medians of C2/C1 M-2 and M-5 ratios were 0.82 (interquartile range 0.50–1.78) and 0.75 (interquartile range 0.41–1.93), respectively. Patients with C2/C1 M-2 ratio ≥ median had improved survival compared to those