Elena Élez1, María Auxiliadora Gómez-España2, Cristina Grávalos3, Pilar García-Alfonso4, María José Ortiz-Morales2, Ferrán Losa5, Inmaculada Alés Díaz6, Begoña Graña7, Marta Toledano-Fonseca8, Manuel Valladares-Ayerbes9, Eduardo Polo10, Mercedes Salgado11, Eva Martínez de Castro12, María José Safont13, Antonieta Salud14, Ana Ruiz-Casado15, Josep Tabernero16, María Del Carmen Riesco3, Antonio Rodriguez-Ariza8, Enrique Aranda17. 1. Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Passeig de la Vall d'Hebron, 119, 08035, Barcelona, Spain. 2. Department of Medical Oncology, IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Avenida Menéndez Pidal, S/N, 14004, Córdoba, Spain. 3. Department of Medical Oncology, H. Universitario 12 de Octubre, Instituto de Investigación i + 12, Avenida de Córdoba, S/N, 28041, Madrid, Spain. 4. Department of Medical Oncology, H. Gregorio Marañón, Calle del Doctor Esquerdo, 46, 28007, Madrid, Spain. 5. Department of Medical Oncology, H. Sant Joan Despí - Moisés Broggi, Carrer d'Oriol Martorell, 12, 08970, Sant Joan Despí, Barcelona, Spain. 6. Department of Medical Oncology, Unidad de Gestión Clínica Intercentros de Oncología Médica. Hospitales Universitarios Regional y Virgen de la Victoria. IBIMA, Campus de Teatinos, S/N, 29010, Málaga, Spain. 7. Department of Medical Oncology, C. H. Universitario, Lugar, Xubias de Arriba, 84, 15006, A Coruña, Spain. 8. Department of Medical Oncology, IMIBIC, Reina Sofía Hospital, CIBERONC, Instituto de Salud Carlos III, Avenida Menéndez Pidal, S/N, 14004, Córdoba, Spain. 9. Department of Medical Oncology, H. Virgen del Rocío, IBIS, Av. Manuel Siurot s/n, 41013, Sevilla, Spain. 10. Department of Medical Oncology, H. Miguel Servet, Paseo Isabel la Católica, 1-3, 50009, Zaragoza, Spain. 11. Department of Medical Oncology, C. H. Universitario de Ourense, Calle Ramón Puga Noguerol, 54, 32005, Orense, Spain. 12. Department of Medical Oncology, H. Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, 25, 39008, Santander, Spain. 13. Department of Medical Oncology, H. General Universitario, CIBERONC, Avenida de les Tres Creus, 2, 46014, Valencia, Spain. 14. Department of Medical Oncology, H. de Lleida Arnau de Vilanova, Avenida Alcalde Rovira Roure, 80, 25198, Lérida, Spain. 15. Department of Medical Oncology, H. Puerta de Hierro Majadahonda, Calle Joaquín Rodrigo, 1, 28222, Majadahonda, Spain. 16. Department of Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), Passeig de la Vall d'Hebron, 119, 08035, Barcelona, Spain. 17. Department of Medical Oncology, IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Avenida Menéndez Pidal, S/N, 14004, Córdoba, Spain. earandaa@seom.org.
Abstract
BACKGROUND: Aflibercept is an antiangiogenic drug against metastatic colorectal cancer (mCRC) combined with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI); however, no antiangiogenic biomarker has yet been validated. We assessed aflibercept plus FOLFIRI, investigating the biomarker role of baseline vascular endothelial growth factor A (VEGF-A) and angiotensin-converting enzyme (ACE). METHODS: Phase II trial in oxaliplatin-treated mCRC patients who received aflibercept plus FOLFIRI. The reported 135 ng/mL ACE cut-off was used and ROC analysis was performed to assess the optimal VEGF-A cut-off for progression-free survival (PFS). Overall survival (OS), time to progression (TTP), time to treatment failure (TTF), overall response rate (ORR) and disease control rate (DCR) were also assessed. RESULTS: In total, 101 patients were followed for a median of 12 (6-17) months. The 1941 pg/mL VEGF-A was an optimal cut-off, with a longer median PFS when VEGF-A was <1941 versus ≥1941 pg/mL (9 versus 4 months). Patients with VEGF-A < 1941 pg/mL showed longer median OS (19 versus 8 months), TTP (9 versus 4 months) and TTF (8 versus 4 months), along with higher ORR (26% versus 9%) and DCR (81% versus 55%). No differences were identified according to ACE levels. CONCLUSIONS: This study supports aflibercept plus FOLFIRI benefits, suggesting VEGF-A as a potential biomarker to predict better outcomes.
BACKGROUND: Aflibercept is an antiangiogenic drug against metastatic colorectal cancer (mCRC) combined with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI); however, no antiangiogenic biomarker has yet been validated. We assessed aflibercept plus FOLFIRI, investigating the biomarker role of baseline vascular endothelial growth factor A (VEGF-A) and angiotensin-converting enzyme (ACE). METHODS: Phase II trial in oxaliplatin-treated mCRC patients who received aflibercept plus FOLFIRI. The reported 135 ng/mL ACE cut-off was used and ROC analysis was performed to assess the optimal VEGF-A cut-off for progression-free survival (PFS). Overall survival (OS), time to progression (TTP), time to treatment failure (TTF), overall response rate (ORR) and disease control rate (DCR) were also assessed. RESULTS: In total, 101 patients were followed for a median of 12 (6-17) months. The 1941 pg/mL VEGF-A was an optimal cut-off, with a longer median PFS when VEGF-A was <1941 versus ≥1941 pg/mL (9 versus 4 months). Patients with VEGF-A < 1941 pg/mL showed longer median OS (19 versus 8 months), TTP (9 versus 4 months) and TTF (8 versus 4 months), along with higher ORR (26% versus 9%) and DCR (81% versus 55%). No differences were identified according to ACE levels. CONCLUSIONS: This study supports aflibercept plus FOLFIRI benefits, suggesting VEGF-A as a potential biomarker to predict better outcomes.
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