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
García-Alfonso, Pilar (Universidad Complutense de Madrid)
Elez, Elena (Hospital Universitari Vall d'Hebron)
Soto-Alsar, Javier (Universidad Complutense de Madrid)
Páez, David (Institut de Recerca Sant Pau)
Fernández Montes, Ana (Complexo Hospitalario Universitario de Ourense - CHUO)
Graña, Begoña (Complejo Hospitalario Universitario de A Coruña)
Salud, Antonia (Hospital Universitari Arnau de Vilanova (Lleida))
Yubero Esteban, Alfonso (Hospital Clínico Universitario "Lozano Blesa" de Zaragoza)
Gómez-España, Maria Auxiliadora (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Macias Declara, Ismael (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Quintero Aldana, Guillermo (Hospital Universitario Lucus Augusti (Lugo))
López-López, Carlos A. (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Fernández-Rodríguez, Teresa (Hospital Universitari Son Llàtzer (Palma de Mallorca, Balears))
Grávalos, Cristina (Hospital Universitario 12 de Octubre (Madrid))
González-Flores, Encarnación (Hospital Universitario Virgen de las Nieves (Granada))
Guix, Marta (Hospital del Mar (Barcelona, Catalunya))
García Paredes, Beatriz (Universidad Complutense de Madrid de Madrid)
Reina-Tosina, Javier (Complejo Hospitalario Virgen de la Macarena)
Rodríguez Mowbray, José Ramón (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Sastre Valera, Javier (Universidad Complutense de Madrid)
Aranda Aguilar, Enrique (Hospital Universitario Reina Sofía (Còrdova, Espanya))

Date:	2024
Abstract:	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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	5-FU ; Aflibercept ; FOLFIRI ; Maintenance treatment ; Metastatic colorectal cancer
Published in:	ESMO open, Vol. 9 Núm. 12 (december 2024) , p. 103986, ISSN 2059-7029

DOI: 10.1016/j.esmoop.2024.103986
PMID: 39608305

9 p, 442.8 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles