A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial) Journal Article
| Authors: | Argilés, G.; Mulet, N.; Valladares-Ayerbes, M.; Viéitez, J. M.; Grávalos, C.; García-Alfonso, P.; Santos, C.; Tobeña, M.; García-Paredes, B.; Benavides, M.; Cano, M. T.; Loupakis, F.; Rodríguez-Garrote, M.; Rivera, F.; Goldberg, R. M.; Cremolini, C.; Bennouna, J.; Ciardiello, F.; Tabernero, J. M.; Aranda, E.; on behalf of the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and UNICANCER GI; The REARRANGE investigators |
| Article Title: | A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial) |
| Abstract: | The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients. 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. 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. 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. NCT02835924. • Feasibility of two dose schedules of regorafenib initial deintensification in Europe. • No improvement on the overall safety profiles was seen. • A reduction in the most relevant AEs was observed (fatigue and HFSR). • Efficacy was sustained across the experimental arms despite dose deintensification. |
| Journal Title: | European Journal of Cancer |
| Volume: | 177 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2022-12-01 |
| Start Page: | 154 |
| End Page: | 163 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2022.09.037 |
| PROVIDER: | EBSCOhost |
| PROVIDER: | cinahl |
| PUBMED: | 36335783 |
| DOI/URL: | |
| Notes: | Accession Number: 160444623 -- Entry Date: In Process -- Revision Date: 20221129 -- Publication Type: Article -- Journal Subset: Biomedical; Blind Peer Reviewed; Editorial Board Reviewed; Europe; Expert Peer Reviewed; Peer Reviewed; UK & Ireland -- NLM UID: 9005373. -- Source: Cinahl |
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