@article{10902/36488,
year = {2024},
url = {https://hdl.handle.net/10902/36488},
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.},
organization = {Funding: This work was supported by Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) (TTD Group), through an unrestricted grant provided by Sanofi (no grant number) Acknowledgments: The authors thank to all the investigators of the AFEMA study. The authors also thank the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD): Inmaculada Ruiz de Mena and Susana Rodríguez. Manuscript writing support was provided by Montse Sabaté-Pina, PhD from TFS},
publisher = {BMJ},
publisher = {ESMO Open, 2024, 9(12), 103986},
title = {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},
author = {García Alfonso P. and Elez E. and Soto Alsar J. and Páez D. and Fernández Montes, A. and Graña, B. and Salud, A. and Yubero, A. and Gómez España, M.A. and Macías, I. and Quintero, G. and López López, Carlos and Fernández Rodríguez T. and Grávalos, C. and González Flores, E. and Guix, M. and García Paredes, B. and Reina, J.J. and Rodríguez Mowbray, J.R. and Sastre, J.},
}