title: FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  NCT01219920 and NCT00719797.
authors: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa.
authors: C
authors: C
authors: Cremolini
authors: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa.
authors: F
authors: F
authors: Loupakis
authors: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa.
authors: G
authors: G
authors: Masi
authors: Unit of Medical Oncology 1, Istituto Oncologico Veneto, IRCSS, Padua.
authors: S
authors: S
authors: Lonardi
authors: Unit of Medical Oncology, Azienda Sanitaria Ospedaliera Santa Croce e Carle, Cuneo.
authors: C
authors: C
authors: Granetto
authors: Department of Medical Oncology, University of Rome La Sapienza, Rome.
authors: M L
authors: ML
authors: Mancini
authors: Department of Medical Oncology 2, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa.
authors: S
authors: S
authors: Chiara
authors: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa.
authors: R
authors: R
authors: Moretto
authors: Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa.
authors: D
authors: D
authors: Rossini
authors: Unit of Oncology, Sant'Elia Hospital, Caltanissetta.
authors: S
authors: S
authors: Vitello
authors: Unit of Medical Oncology, 'Felice Lotti' Hospital, Pontedera.
authors: G
authors: G
authors: Allegrini
authors: Department of Medical Oncology, University Campus Biomedico, Rome.
authors: G
authors: G
authors: Tonini
authors: Unit of Medical Oncology 1, Istituto Oncologico Veneto, IRCSS, Padua.
authors: F
authors: F
authors: Bergamo
authors: Division of Medicine and Medical Oncology, Azienda Istituti Ospitalieri, Cremona.
authors: G
authors: G
authors: Tomasello
authors: Department of Oncology, 'San Raffaele' Hospital IRCSS, Milan.
authors: M
authors: M
authors: Ronzoni
authors: Division of Oncology, Centro di Riferimento Oncologico, Aviano.
authors: A
authors: A
authors: Buonadonna
authors: ColoRectal Cancer Unit, Unit of Oncology 1, 'Molinette' Hospital, Città della Salute e della Scienza, Turin.
authors: S
authors: S
authors: Bustreo
authors: Unit of Medical Oncology, Spedali Riuniti di Livorno, Livorno.
authors: C
authors: C
authors: Barbara
authors: Clinical Trials Coordinating Center, Istituto Toscano Tumori, Florence, Italy.
authors: L
authors: L
authors: Boni
authors: 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.
authors: A
authors: A
authors: Falcone
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: FOLFOXIRI; bevacizumab; metastatic colorectal cancer