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, Guillem Argilés, Nuria Mulet, Manuel Valladares‐Ayerbes, J.M. Viéitez, Cristina Grávalos, Pilar García‐Alfonso, Cristina Santos, M. Tobeña, Beatriz García-Paredes, Manuel Benavides, María Teresa Cano, Fotios Loupakis, Mercedes Rodríguez-Garrote, Fernando Rivera, Richard M. Goldberg, Chiara Cremolini, Jaafar Bennouna, Fortunato Ciardiello, Josep Tabernero, Enrique Aranda, Josep Tabernero, Guillem Argilés, Guillem Argilés, Alfredo Falcone, Fortunato Ciardiello, Richard M. Goldberg, Jaafar Bennouna, Argilés, Josep Tabernero, Nuria Mulet, M. Luisa Limon, M. Valladares, Pedro Jiménez, J.M. Viéitez, Cristina Grávalos, Pilar García‐Alfonso, Cristina Santos, David Páez, M. Tobeña, Javier Sastre, Beatriz Paredes, Manuel Benavides, Enrique Aranda, María Teresa Cano, Fotios Loupakis, M. Rguez Garrote, C. Guillén, Ma F. Rivera, Joan Andreu Safont, Sandrine Hiret, Jaafar Bennouna, Diane Pannier, David Malka, Alfredo Falcone, Chiara Cremolini, Guillem Argilés, Guillem Argilés, Josep Tabernero
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.