A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial)
Por:
Argilés G., Valladares-Ayerbes M., Viéitez J.M., García-Paredes B., Rodríguez-Garrote M., Rivera F., Goldberg R.M., Ciardiello F., Tabernero J.M., Goldberg R., Argilés, Tabernero J., Mulet N., Limón M.L., Valladares M., Jiménez P., Vieitez J.M., Grávalos C., García-Alfonso P., Santos C., Páez D., Tobeña M., Sastre J., García Paredes B., Benavides M., Aranda E., Cano M.T., Loupakis F., Rguez Garrote M., Guillén C., Rivera M.F., Safont J., Hiret S., Bennouna J., Pannier D., Malka D., Falcone A., Cremolini C., The
Publicada:
1 ene 2022
Resumen:
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. Clinicaltrials.gov identifier: NCT02835924. © 2022 The Author(s)
Filiaciones:
Argilés G.:
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), CIBERONC, Barcelona, Spain
Universitat Autònoma de Barcelona, Barcelona, Spain
Memorial Sloan Kettering Cancer Center, New York, United States
Valladares-Ayerbes M.:
Virgen del Rocío University Hospital and Institute of Biomedicine (IBIS), Sevilla, Spain
Viéitez J.M.:
Hospital Universitario Central de Asturias, Oviedo, Spain
García-Paredes B.:
Clínico San Carlos Hospital, Instituto de Investigación Hospital Clinico San Carlos (IdISSC) CIBERONC, Madrid, Spain
H. Universitario Clínico San Carlos, Madrid, Spain
Rodríguez-Garrote M.:
Ramon y Cajal University Hospital-IRYCIS, CIBERONC, Alcalá University, Madrid, Spain
Rivera F.:
University Hospital Marqués de Valdecilla (IDIVAL) Santander, Spain
Goldberg R.M.:
West Virgina University Cancer Institute, Morgantown, United States
Ciardiello F.:
Università della Campania L. Vanvitelli, Italy
Tabernero J.M.:
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), CIBERONC, Barcelona, Spain
Goldberg R.:
West Virgina University Cancer Institute, Morgantown, United States
Argilés:
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), CIBERONC, Barcelona, Spain
Universitat Autònoma de Barcelona, Barcelona, Spain
Memorial Sloan Kettering Cancer Center, New York, United States
Tabernero J.:
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), CIBERONC, Barcelona, Spain
Mulet N.:
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), CIBERONC, Barcelona, Spain
Memorial Sloan Kettering Cancer Center, New York, United States
Limón M.L.:
H. Virgen del Rocío, Sevilla, Spain
Valladares M.:
H. Virgen del Rocío, Sevilla, Spain
Jiménez P.:
H. Universitario Central de Asturias, Spain
Vieitez J.M.:
H. Universitario Central de Asturias, Spain
Grávalos C.:
Universitary Hospital 12 de Octubre, Madrid, Spain
García-Alfonso P.:
Gregorio Marañón Hospital, Madrid, Spain
Santos C.:
Institute Català d'Oncologia (ICO), Duran i Reynals Hospital – ONCOBELL, CIBERONC, Barcelona, Spain
Páez D.:
H. Santa Creu i Sant Pau, Barcelona, Spain
Tobeña M.:
Santa Creu I Sant Pau Hospital, Barcelona, Spain
H. Santa Creu i Sant Pau, Barcelona, Spain
Sastre J.:
H. Universitario Clínico San Carlos, Madrid, Spain
García Paredes B.:
Clínico San Carlos Hospital, Instituto de Investigación Hospital Clinico San Carlos (IdISSC) CIBERONC, Madrid, Spain
H. Universitario Clínico San Carlos, Madrid, Spain
Benavides M.:
Regional University Hospital, Málaga, Spain
Aranda E.:
Regional University Hospital, Málaga, Spain
Cano M.T.:
IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Spain
Loupakis F.:
Istituto oncologico Veneto, Italy
Rguez Garrote M.:
H. Ramón y Cajal, Madrid, Spain
Guillén C.:
H. Ramón y Cajal, Madrid, Spain
Rivera M.F.:
H. Marqués de Valdecilla, Santander, Spain
Safont J.:
H. General Universitario, Valencia, Spain
Hiret S.:
Institut de Cancérologie de l'Ouest, France
Bennouna J.:
University Hospital of Nantes, Digestive Oncology, Nantes, France
Pannier D.:
Centre Oscar Lambret, France
Malka D.:
Gustave Roussy, France
Cremolini C.:
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
All Open Access; Green
|