A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial).

Purpose: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients.
Patients and Methods: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm.
Results: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C.
Conclusions: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles.
Gov Identifier: NCT02835924.
Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: G. Argilés received advisory honoraria, from Gadetta BV. Amgen, Bayer and Servier; M. Valladares-Ayerbes received honoraria, travel grants, and research grants from Hoffman La Roche, Bristol-Myers Squibb, Bayer, Servier, Amgen, Merck Serono and Sanofi. N. Mulet received grants and non-financial support from Merck Serono, Amgen and Roche, outside the submitted work; M. Tobeña received personal fees from Amgen, Kyowa Kirin and Grunenthal, non-financial support from Merck, Roche and Rovi, outside the submitted work; B. García received personal fees from Advanced Accelerator Applications (a Novartis company), Amgen, Bayer Hispania, Eisai, Lilly, MSD and Roche Farma, personal fees and non-financial support from Ipsen, Merck, Novartis, Sanofi-Aventis and Servier, outside the submitted work; E. Aranda received honoraria for advisory role from Amgen, Bayer, Celgene, Merck, Roche and Sanofi; C. Cremolini received honoraria for Advisory Board/Speaker from Amgen, Bayer, Merck, MSD, Roche, Servier and Research, grants from Bayer, Roche and Servier. The other authors have stated that they have no conflicts of interest.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)