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
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....
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2024 |
| Country: | España |
| Institution: | Institut d'Investigació i Innovació Parc Taulí (I3PT) |
| Repository: | r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí |
| OAI Identifier: | oai:i3pt.fundanetsuite.com:p5379 |
| Online Access: | https://i3pt.portalinvestigacion.com/publicaciones/5379 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85210056180&doi=10.1016%2fj.esmoop.2024.103986&partnerID=40&md5=35570cac4b2551f81d190f7fcb1ba44e |
| Access Level: | Open access |
| Keyword: | metastatic colorectal cancer aflibercept FOLFIRI 5-FU maintenance treatment |
| _version_ | 1878738160049979392 |
|---|---|
| author | García-Alfonso, P |
| author2 | 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 |
| author2_role | author author author author author author author author author author author author author author author author author author author author |
| author_browse | Aranda, E Elez, E Fernández-Montes, A Fernández-Rodríguez, T García-Alfonso, P González-Flores, E Graña, B Grávalos, C Guix, M Gómez-España, MA López-López, C Macías, I Mowbray, JRR Paredes, BG Páez, D Quintero, G Reina, JJ Salud, A Sastre, J Soto-Alsar, J Yubero, A |
| author_facet | 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 |
| author_role | author |
| collection | r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_aa8d7d8513ba3f1d5c45648203c2a82f |
| institution | Institut d'Investigació i Innovació Parc Taulí (I3PT) |
| instname_str | Institut d'Investigació i Innovació Parc Taulí (I3PT) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:i3pt.fundanetsuite.com:p5379 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | ELSEVIER |
| publisherStr | ELSEVIER |
| reponame_str | r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí |
| spelling | 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, 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 metastatic colorectal cancer aflibercept FOLFIRI 5-FU maintenance treatment 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. ELSEVIER https://i3pt.portalinvestigacion.com/publicaciones/5379 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85210056180&doi=10.1016%2fj.esmoop.2024.103986&partnerID=40&md5=35570cac4b2551f81d190f7fcb1ba44e |
| spellingShingle | 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, P metastatic colorectal cancer aflibercept FOLFIRI 5-FU maintenance treatment |
| status_str | publishedVersion |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | metastatic colorectal cancer aflibercept FOLFIRI 5-FU maintenance treatment |
| topic_facet | metastatic colorectal cancer aflibercept FOLFIRI 5-FU maintenance treatment |
| url | https://i3pt.portalinvestigacion.com/publicaciones/5379 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85210056180&doi=10.1016%2fj.esmoop.2024.103986&partnerID=40&md5=35570cac4b2551f81d190f7fcb1ba44e |