Abstract
BackgroundRegorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor receptor. A dose reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated adverse events (AEs). Dose adjustment of irinotecan in a 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) regimen on the basis of an individual uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotype provides optimal oncological outcomes with acceptable AEs. The aim of this study is to address the efficacy and safety of a dose-adjusted combination of regorafenib and FOLFIRI for patients with mCRC.MethodsA prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose-escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with mCRC. The primary endpoint is progression-free survival, and the secondary endpoints are overall survival, disease control rate, time to progression, and duration of treatment. Safety assessments will also be recorded.DiscussionDose adjustment for regorafenib and irinotecan makes treatment-related AEs tolerable and makes the concomitant treatment practicable. This study will provide initial evidence regarding the efficacy and safety of a new combination of chemotherapy and a targeted agent for mCRC.Trial registrationClinicalTrials.gov, NCT03880877. Prospectively registered on 19 March 2019.
Highlights
Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor receptor
In our previous preliminary observational study, in which regorafenib plus FOLFIRI with dose escalation according to uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotype were administered to previously treated patients with metastatic colorectal cancer (mCRC), we revealed superior oncological effects over regorafenib monotherapy [9]
The current study aims to explore the efficacy and safety of regorafenib and FOLFIRI concomitant treatment with dose-adjusted irinotecan based on UGT1A1 genotype in previously treated mCRC patients compared to those who receive regorafenib alone in a prospective, randomized, twoarm, controlled setting
Summary
Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor receptor. A dose reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated adverse events (AEs). Regorafenib monotherapy is currently the third- or fourth-line standard of care for patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidines, irinotecan, oxaliplatin, and monoclonal antibodies targeting vascular endothelial growth factor (VEGF), and monoclonal antibodies targeting epidermal growth factor receptor (EGFR) for those with KRAS wild-type cancers. Dose reduction of regorafenib to 120 mg reduces the severity of AEs and allows better patient tolerance and compliance with comparable oncological results [4]
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