C Cremolini1, F Loupakis1, G Masi1, S Lonardi2, C Granetto3, M L Mancini4, S Chiara5, R Moretto1, D Rossini1, S Vitello6, G Allegrini7, G Tonini8, F Bergamo2, G Tomasello9, M Ronzoni10, A Buonadonna11, S Bustreo12, C Barbara13, L Boni14, A Falcone15. 1. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa. 2. Unit of Medical Oncology 1, Istituto Oncologico Veneto, IRCSS, Padua. 3. Unit of Medical Oncology, Azienda Sanitaria Ospedaliera Santa Croce e Carle, Cuneo. 4. Department of Medical Oncology, University of Rome La Sapienza, Rome. 5. Department of Medical Oncology 2, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa. 6. Unit of Oncology, Sant'Elia Hospital, Caltanissetta. 7. Unit of Medical Oncology, 'Felice Lotti' Hospital, Pontedera. 8. Department of Medical Oncology, University Campus Biomedico, Rome. 9. Division of Medicine and Medical Oncology, Azienda Istituti Ospitalieri, Cremona. 10. Department of Oncology, 'San Raffaele' Hospital IRCSS, Milan. 11. Division of Oncology, Centro di Riferimento Oncologico, Aviano. 12. ColoRectal Cancer Unit, Unit of Oncology 1, 'Molinette' Hospital, Città della Salute e della Scienza, Turin. 13. Unit of Medical Oncology, Spedali Riuniti di Livorno, Livorno. 14. Clinical Trials Coordinating Center, Istituto Toscano Tumori, Florence, Italy. 15. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa alfredo.falcone@med.unipi.it.
Abstract
BACKGROUND:FOLFOXIRI plus bevacizumab is a valid option as upfront treatment for metastatic colorectal cancer (mCRC) patients. While several trials investigated the effect of combining bevacizumab with different chemotherapy regimens, including fluoropyrimidines monotherapy and oxaliplatin- or irinotecan-containing doublets, no randomized comparison assessing the impact of the addition of bevacizumab to FOLFOXIRI is available. PATIENTS AND METHODS: A total of 122 mCRC patients received first-line FOLFOXIRI in the phase III trial by the GONO (FOLFOXIRI group) and 252 patients receivedfirst-line FOLFOXIRI plus bevacizumab in the TRIBE trial (FOLFOXIRI plus bevacizumab group). A propensity score-adjusted method was adopted to provide an estimation of the benefit from the addition of bevacizumab to FOLFOXIRI in terms of survival and activity parameters. RESULTS: Patients in the FOLFOXIRI group had more frequently Eastern Cooperative Oncology Group performance status of one or two, high Köhne score, metachronous and liver-limited disease, had previously received adjuvant treatments and had their primary tumors resected. The median progression-free survival (PFS) was 12.3 months in the FOLFOXIRI plus bevacizumab group compared with 10.0 months in the FOLFOXIRI group {propensity score-adjusted hazard ratio (HR) 0.74 [95% confidence interval (CI) 0.59-0.94], P = 0.013}. This association was significant also in the multivariable model (P = 0.024). The median OS was 29.8 months in the FOLFOXIRI plus bevacizumab group compared with 23.6 months in the FOLFOXIRI group [propensity score-adjusted HR: 0.72 (95% CI 0.56-0.93), P = 0.014]. At the multivariable model, the addition of bevacizumab was still associated with significantly longer OS (P = 0.030). No significant differences in RECIST response rate (RR) [65.1% versus 55.7%; propensity score-adjusted odds ratio (OR): 1.29 (95% CI 0.81-2.05), P = 0.280], early RR [62.7% versus 57.8%; OR: 1.14 (95% CI 0.68-1.93), P = 0.619] and median depth of response (42.2% versus 53.8%, P = 0.259) were reported. CONCLUSIONS: Though in the absence of a randomized comparison, the addition of bevacizumab to FOLFOXIRI provides significant benefit in PFS and OS, thus supporting the use of FOLFOXIRI plus bevacizumab as upfront treatment for mCRC patients. TRIALS' NUMBERS: NCT01219920 and NCT00719797.
RCT Entities:
BACKGROUND:FOLFOXIRI plus bevacizumab is a valid option as upfront treatment for metastatic colorectal cancer (mCRC) patients. While several trials investigated the effect of combining bevacizumab with different chemotherapy regimens, including fluoropyrimidines monotherapy and oxaliplatin- or irinotecan-containing doublets, no randomized comparison assessing the impact of the addition of bevacizumab to FOLFOXIRI is available. PATIENTS AND METHODS: A total of 122 mCRC patients received first-line FOLFOXIRI in the phase III trial by the GONO (FOLFOXIRI group) and 252 patients received first-line FOLFOXIRI plus bevacizumab in the TRIBE trial (FOLFOXIRI plus bevacizumab group). A propensity score-adjusted method was adopted to provide an estimation of the benefit from the addition of bevacizumab to FOLFOXIRI in terms of survival and activity parameters. RESULTS:Patients in the FOLFOXIRI group had more frequently Eastern Cooperative Oncology Group performance status of one or two, high Köhne score, metachronous and liver-limited disease, had previously received adjuvant treatments and had their primary tumors resected. The median progression-free survival (PFS) was 12.3 months in the FOLFOXIRI plus bevacizumab group compared with 10.0 months in the FOLFOXIRI group {propensity score-adjusted hazard ratio (HR) 0.74 [95% confidence interval (CI) 0.59-0.94], P = 0.013}. This association was significant also in the multivariable model (P = 0.024). The median OS was 29.8 months in the FOLFOXIRI plus bevacizumab group compared with 23.6 months in the FOLFOXIRI group [propensity score-adjusted HR: 0.72 (95% CI 0.56-0.93), P = 0.014]. At the multivariable model, the addition of bevacizumab was still associated with significantly longer OS (P = 0.030). No significant differences in RECIST response rate (RR) [65.1% versus 55.7%; propensity score-adjusted odds ratio (OR): 1.29 (95% CI 0.81-2.05), P = 0.280], early RR [62.7% versus 57.8%; OR: 1.14 (95% CI 0.68-1.93), P = 0.619] and median depth of response (42.2% versus 53.8%, P = 0.259) were reported. CONCLUSIONS: Though in the absence of a randomized comparison, the addition of bevacizumab to FOLFOXIRI provides significant benefit in PFS and OS, thus supporting the use of FOLFOXIRI plus bevacizumab as upfront treatment for mCRC patients. TRIALS' NUMBERS: NCT01219920 and NCT00719797.
Authors: Aurélien Dupré; Robert P Jones; Rafael Diaz-Nieto; Stephen W Fenwick; Graeme J Poston; Hassan Z Malik Journal: World J Surg Date: 2019-05 Impact factor: 3.352
Authors: Herbert I Hurwitz; Benjamin R Tan; James A Reeves; Henry Xiong; Brad Somer; Heinz-Josef Lenz; Howard S Hochster; Frank Scappaticci; John F Palma; Richard Price; John J Lee; Alan Nicholas; Nicolas Sommer; Johanna Bendell Journal: Oncologist Date: 2018-12-14
Authors: Eric Van Cutsem; Sanne Huijberts; Axel Grothey; Rona Yaeger; Pieter-Jan Cuyle; Elena Elez; Marwan Fakih; Clara Montagut; Marc Peeters; Takayuki Yoshino; Harpreet Wasan; Jayesh Desai; Fortunato Ciardiello; Ashwin Gollerkeri; Janna Christy-Bittel; Kati Maharry; Victor Sandor; Jan H M Schellens; Scott Kopetz; Josep Tabernero Journal: J Clin Oncol Date: 2019-03-20 Impact factor: 44.544