Daniele Rossini1,2, Sara Lonardi3, Carlotta Antoniotti1,2, Daniele Santini4, Gianluca Tomasello5, Paola Ermacora6, Marco Maria Germani1,2, Francesca Bergamo3, Vincenzo Ricci7, Salvatore Caponnetto8, Roberto Moretto2, Alberto Zaniboni9, Filippo Pietrantonio10,11, Angela Buonadonna12, Giuliana Ritorto13, Gianluca Masi1,2, Tiziana Pia Latiano14, Stefania Rapisardi15, Alfredo Falcone1,2, Chiara Cremolini16,17. 1. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. 2. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 3. Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Veneto Institute of Oncology, IOV - IRCSS, Via Gattamelata 64, 35128, Padova, Italy. 4. Department of Medical Oncology, Campus Bio-Medico-University of Rome, Via Álvaro del Portillo 200, 00128, Rome, Italy. 5. Oncology Unit, Oncology Department, ASST of Cremona, Viale Concordia 1, 26100, Cremona, Italy. 6. Department of Oncology, ASUFC University Hospital, Udine, Via Pozzuolo 330, 33100, Udine, Italy. 7. Medical Oncology and Laboratory of Translational Oncology, Oncology Department, S. Croce and Carle Teaching Hospital Cuneo, Via Michele Coppino 26, 12100, Cuneo, Italy. 8. Department of Radiological Science, Oncology And Pathology, Policlinico Umberto I, "Sapienza" University of Rome, Viale del Policlinico 155, 00161, Rome, Italy. 9. Medical Oncology Unit, Poliambulanza Foundation, Via Bissolati 57, 25124, Brescia, Italy. 10. Medical Oncology Department, Fondazione IRCSS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy. 11. Department of Oncology and Hemato-oncology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy. 12. Department of Clinical Oncology, Centro di Riferimento Oncologico (CRO) IRCCS, Via Franco Gallini 2, 33081, Aviano, Italy. 13. Ssd Colorectal Cancer Unit Dipartimento Di Oncologia, AOU Città della Salute e della Scienza di Torino, Corso Bramante 88, 10126, Turin, Italy. 14. Oncology Unit, IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71013, San Giovanni Rotondo, Italy. 15. Oncology Unit, ARNAS Garibaldi Catania, Piazza Santa Maria di Gesù 5, 95100, Catania, Italy. 16. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. chiaracremolini@gmail.com. 17. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. chiaracremolini@gmail.com.
Abstract
BACKGROUND:FOLFOXIRI/bevacizumab (bev) is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer. The upfront exposure to three cytotoxics raises concerns about the efficacy of treatments after progression. METHODS: We performed a pooled analysis of treatments after progression to upfront FOLFOXIRI/bev in patients enrolled in two randomised Phase 3 studies (TRIBE and TRIBE2) that compared FOLFOXIRI/bev to doublets (FOLFOX or FOLFIRI)/bev. Response rate, progression-free survival (2nd PFS) and overall survival (2nd OS) during treatments after progression were assessed. The RECIST response in first line and the oxaliplatin and irinotecan-free interval (OIFI) were investigated as potential predictors of benefit from FOLFOXIRI ± bev reintroduction. RESULTS: Longer 2nd PFS was reported in patients receiving FOLFOXIRI ± bev reintroduction compared to doublets ± bev or other treatments (6.1 versus 4.4 and 3.9 months, respectively, P = 0.013), and seems limited to patients achieving a response during first line (6.9 versus 4.2 and 4.7 months, respectively, P = 0.005) and an OIFI ≥ 4 months (7.2 versus 6.5 and 4.6 months, respectively, P = 0.045). CONCLUSIONS: First-line FOLFOXIRI/bev does not impair the administration of effective second-line therapies. First-line response and longer OIFI seem associated with improved response and 2nd PFS from FOLFOXIRI ± bev reintroduction, without impacting 2nd OS.
RCT Entities:
BACKGROUND: FOLFOXIRI/bevacizumab (bev) is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer. The upfront exposure to three cytotoxics raises concerns about the efficacy of treatments after progression. METHODS: We performed a pooled analysis of treatments after progression to upfront FOLFOXIRI/bev in patients enrolled in two randomised Phase 3 studies (TRIBE and TRIBE2) that compared FOLFOXIRI/bev to doublets (FOLFOX or FOLFIRI)/bev. Response rate, progression-free survival (2nd PFS) and overall survival (2nd OS) during treatments after progression were assessed. The RECIST response in first line and the oxaliplatin and irinotecan-free interval (OIFI) were investigated as potential predictors of benefit from FOLFOXIRI ± bev reintroduction. RESULTS: Longer 2nd PFS was reported in patients receiving FOLFOXIRI ± bev reintroduction compared to doublets ± bev or other treatments (6.1 versus 4.4 and 3.9 months, respectively, P = 0.013), and seems limited to patients achieving a response during first line (6.9 versus 4.2 and 4.7 months, respectively, P = 0.005) and an OIFI ≥ 4 months (7.2 versus 6.5 and 4.6 months, respectively, P = 0.045). CONCLUSIONS: First-line FOLFOXIRI/bev does not impair the administration of effective second-line therapies. First-line response and longer OIFI seem associated with improved response and 2nd PFS from FOLFOXIRI ± bev reintroduction, without impacting 2nd OS.
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