Maintenance with 5-FU/LV-aflibercept after induction with FOLFIRI-aflibercept versus FOLFIRI-aflibercept until progression as second-line treatment in older adults with metastatic colorectal cancer: the AFEMA phase II randomized trial.

Autor:	García-Alfonso P; Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, Madrid, Spain. Electronic address: pgarcaalfonso@gmail.com., Elez E; Medical Oncology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, CIBERONC, Barcelona, Spain., Soto-Alsar J; Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense, Madrid, Spain., Páez D; Department of Medical Oncology, Hospital Santa Creu i Sant Pau, U705 CIBERER, Barcelona, Spain., Fernández-Montes A; Department of Medical Oncology, Complexo Hospitalario Universitario de Ourense, Ourense, Spain., Graña B; Department of Medical Oncology, Complexo Hospitalario Universitario A Coruña, Instituto Investigación Biomédica INIBIC, A Coruña, Spain., Salud A; Department of Medical Oncology, Hospital Universitario Arnau de Vilanova de Lleida, Lleida, Spain., Yubero A; Department of Medical Oncology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain., Gómez-España MA; Department of Medical Oncology IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain., Macías I; Department of Medical Oncology, Hospital Parc Taulí de Sabadell, Barcelona, Spain., Quintero G; Department of Medical Oncology, Hospital Lucus Augusti, Lugo, Spain., López-López C; Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, IDIVAL, UNICAN, Santander, Spain., Fernández-Rodríguez T; Department of Medical Oncology, Hospital Son Llatzer, Palma de Mallorca, Spain., Grávalos C; Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., González-Flores E; Department of Medical Oncology, Hospital Virgen de las Nieves, Granada, Spain., Guix M; Department of Medical Oncology, Hospital del Mar, Barcelona, Spain., García Paredes B; Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), Universidad Complutense, Madrid, Spain., Reina JJ; Department of Medical Oncology, Complejo Hospitalario Virgen de la Macarena, Sevilla, Spain., Rodríguez Mowbray JR; Department of Medical Oncology, Hospital Virgen del Rocío, Sevilla, Spain., Sastre J; Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), Universidad Complutense, Madrid, Spain., Aranda E; Department of Medical Oncology IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2024 Dec; Vol. 9 (12), pp. 103986. Date of Electronic Publication: 2024 Nov 27.
DOI:	10.1016/j.esmoop.2024.103986
Abstrakt:	Background: The combination chemotherapy i.v. 5-fluorouracil (5-FU), irinotecan, and aflibercept (FOLFIRI-A) is a standard second-line treatment of metastatic colorectal cancer (mCRC). The aim was to assess maintenance treatment in second-line setting in older patients (aged ≥70 years) with mCRC. Patients and Methods: We evaluated FOLFIRI-A given for six cycles followed by maintenance with 5-FU/leucovorin (LV)-A (arm A) or FOLFIRI-A (arm B) until progression in older adults with mCRC in the AFEMA randomized, open-label, non-inferiority phase II trial (EudraCT2016-004076-21/NCT03279289). Patients aged ≥70 years who previously failed oxaliplatin-fluoropyrimidine were randomly allocated (1 : 1) to either arm A (experimental) or arm B (control). After enrolling 35 patients, the FOLFIRI dose was reduced to level 1 in both arms due to toxicity. The primary endpoint was median progression-free survival (PFS); and secondary endpoints were median overall survival, objective response rate, and safety. Non-inferiority required the upper confidence interval (CI) limit to not exceed a hazard ratio (HR) of 1.5 (one-sided α = 0.075, 80% power). Results: A total of 170 patients were randomly allocated to arm A or arm B (n = 85 each). The median follow-up was 12.2 versus 10.9 months in arm A versus arm B. Most patients died (83.5% versus 88.2% in arm A versus arm B), mainly from disease progression. PFS non-inferiority was met (HR = 0.78, 95% CI 0.566-1.076, P = 0.131) with a median PFS of 6.1 versus 5.5 months in arm A versus arm B. Median overall survival was similar in arms A and B (12.2 and 11.5 months, respectively) (HR = 0.89, 95% CI 0.640-1.227, P = 0.467). During the maintenance phase, severe asthenia (4.5% versus 21.6%, P = 0.038), serious adverse events (SAEs) (17.8% versus 37.8%, P = 0.049), and treatment-related SAEs (6.7% versus 10.8%, P = 0.695) were reduced in arm A versus arm B. Conclusion: In older adults, induction with six cycles of FOLFIRI-A plus maintenance with 5-FU/LV-A was non-inferior to FOLFIRI-A until progression. Severe asthenia, SAEs, and treatment-related SAEs were reduced with 5-FU/LV-A maintenance. (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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