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
Por:
García-Alfonso, P, Elez, E, Soto-Alsar, J, Páez, D, Fernández-Montes, A, Graña, B, Salud, A, Yubero, A, Gómez-España, MA, Macías, I, Quintero, G, López-López, C, Fernández-Rodríguez, T, Grávalos, C, González-Flores, E, Guix, M, Paredes, BG, Reina, JJ, Mowbray, JRR, Sastre, J, Aranda, E
Publicada:
1 dic 2024
Resumen:
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, noninferiority 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 alpha=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 treatmentrelated 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.
Filiaciones:
García-Alfonso, P:
Univ Complutense, Hosp Gen Univ Gregorio Maranon, Med Oncol Dept, Madrid, Spain
Elez, E:
Univ Autonoma Barcelona, Med Oncol Dept, Hosp Univ Vall dHebron, Vall dHebron Inst Oncol VHIO,CIBERONC, Barcelona, Spain
Soto-Alsar, J:
Univ Complutense, Hosp Gen Univ Gregorio Maranon, Med Oncol Dept, Madrid, Spain
Páez, D:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, U705 CIBERER, Barcelona, Spain
Fernández-Montes, A:
Complexo Hosp Univ Ourense, Dept Med Oncol, Orense, Spain
Graña, B:
Complexo Hosp Univ A Coruna, Dept Med Oncol, Inst Invest Biomed INIBIC, La Coruna, Spain
Salud, A:
Hosp Univ Arnau de Vilanova Lleida, Dept Med Oncol, Lleida, Spain
Yubero, A:
Hosp Clin Univ Lozano Blesa, Dept Med Oncol, Zaragoza, Spain
Gómez-España, MA:
Univ Cordoba, Hosp Univ Reina Sofia, Dept Med Oncol IMIBIC, CIBERONC,Inst Salud Carlos III, Cordoba, Spain
Macías, I:
Hosp Parc Tauli Sabadell, Dept Med Oncol, Barcelona, Spain
Quintero, G:
Hosp Lucus Augusti, Dept Med Oncol, Lugo, Spain
López-López, C:
Hosp Univ Marques de Valdecilla, Med Oncol Dept, IDIVAL, UNICAN, Santander, Spain
Fernández-Rodríguez, T:
Hosp Son Llatzer, Dept Med Oncol, Palma De Mallorca, Spain
Grávalos, C:
Hosp Univ 12 Octubre, Dept Med Oncol, Madrid, Spain
González-Flores, E:
Hosp Virgen de las Nieves, Dept Med Oncol, Granada, Spain
Guix, M:
Hosp Mar, Dept Med Oncol, Barcelona, Spain
Paredes, BG:
Univ Complutense, Inst Invest Hosp Clin San Carlos IdISSC, Hosp Clin San Carlos, Dept Med Oncol, Madrid, Spain
Reina, JJ:
Complejo Hosp Virgen de la Macarena, Dept Med Oncol, Seville, Spain
Mowbray, JRR:
Hosp Univ Virgen del Rocio, Dept Med Oncol, Seville, Spain
Sastre, J:
Univ Complutense, Inst Invest Hosp Clin San Carlos IdISSC, Hosp Clin San Carlos, Dept Med Oncol, Madrid, Spain
Aranda, E:
Univ Cordoba, Hosp Univ Reina Sofia, Dept Med Oncol IMIBIC, CIBERONC,Inst Salud Carlos III, Cordoba, Spain
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