A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial)
Guillem Argilés, Nuria Mulet, Manuel Valladares-Ayerbes, José M Viéitez, Cristina Grávalos, Pilar García-Alfonso, Cristina Santos, María Tobeña, Beatriz García-Paredes, Manuel Benavides, María T Cano, Fotios Loupakis, Mercedes Rodríguez-Garrote, Fernando Rivera, Richard M Goldberg, Chiara Cremolini, Jaafar Bennouna, Fortunato Ciardiello, Josep M Tabernero, Enrique Aranda, Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and UNICANCER GI, The, REARRANGE investigators, Principal investigator, Guillem Argilés, Josep Tabernero, Steering Committee, Investigators, Josep Tabernero, Guillem Argilés, Alfredo Falcone, Fortunato Ciardiello, Richard Goldberg, Jaafar Bennouna, Argilés, J Tabernero, N Mulet, M L Limón, M Valladares, P Jiménez, J Ma Vieitez, C Grávalos, P García-Alfonso, C Santos, D Páez, M Tobeña, J Sastre, B García Paredes, M Benavides, E Aranda, M T Cano, F Loupakis, M Rguez Garrote, C Guillén, Ma F Rivera, J Safont, S Hiret, J Bennouna, D Pannier, D Malka, A Falcone, C Cremolini, Guillem Argilés, Nuria Mulet, Manuel Valladares-Ayerbes, José M Viéitez, Cristina Grávalos, Pilar García-Alfonso, Cristina Santos, María Tobeña, Beatriz García-Paredes, Manuel Benavides, María T Cano, Fotios Loupakis, Mercedes Rodríguez-Garrote, Fernando Rivera, Richard M Goldberg, Chiara Cremolini, Jaafar Bennouna, Fortunato Ciardiello, Josep M Tabernero, Enrique Aranda, Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and UNICANCER GI, The, REARRANGE investigators, Principal investigator, Guillem Argilés, Josep Tabernero, Steering Committee, Investigators, Josep Tabernero, Guillem Argilés, Alfredo Falcone, Fortunato Ciardiello, Richard Goldberg, Jaafar Bennouna, Argilés, J Tabernero, N Mulet, M L Limón, M Valladares, P Jiménez, J Ma Vieitez, C Grávalos, P García-Alfonso, C Santos, D Páez, M Tobeña, J Sastre, B García Paredes, M Benavides, E Aranda, M T Cano, F Loupakis, M Rguez Garrote, C Guillén, Ma F Rivera, J Safont, S Hiret, J Bennouna, D Pannier, D Malka, A Falcone, C Cremolini
Abstract
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.
Keywords: Colorectal cancer; Drug administration schedule; Metastasis; Regorafenib.
Conflict of interest statement
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.
Source: PubMed