title: The impact of bevacizumab in metastatic colorectal cancer with an intact primary tumor: Results from a large prospective cohort study.
abstract: BACKGROUND
  Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood.
  
  
  METHODS
  Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed.
  
  
  RESULTS
  Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs 17.3 months, P = 0.004)).1Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623.1CONCLUSIONS: The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes.
authors.affiliation: Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.|Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.|Faculty of Medicine, Dentistry & Health Sciences University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Lee
authors.affiliation: Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.|Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.|Faculty of Medicine, Dentistry & Health Sciences University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Wong
authors.affiliation: Faculty of Medicine, Dentistry & Health Sciences University of Melbourne, Melbourne, VIC, Australia.|Melbourne EpiCenter, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Tacey
authors.affiliation: Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.|Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.|Western Health, Department of Medical Oncology, Boxhill, TAS, Australia.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Tie
authors.affiliation: Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.|Eastern Health, Department of Medical Oncology, Boxhill, TAS, Australia.|Monash University, Department of Medicine, Nursing and Health Sciences, Hobart, TAS, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wong
authors.affiliation: Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.|Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.|Eastern Health, Department of Medical Oncology, Boxhill, TAS, Australia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Lee
authors.affiliation: Royal Hobart Hospital, Department of Medical Oncology, Hobart, TAS, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Nott
authors.affiliation: Monash University, Department of Medicine, Nursing and Health Sciences, Hobart, TAS, Australia.|Cabrini Health, Department of Medical Oncology, Malvern, VIC, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Shapiro
authors.affiliation: Epworth Hospital, Department of Medical Oncology, Richmond, VIC, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Jennens
authors.affiliation: Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.|Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Turner
authors.affiliation: Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.|Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Tran
authors.affiliation: Western Health, Department of Medical Oncology, Boxhill, TAS, Australia.
authors.forename: Sumitra
authors.initials: S
authors.lastname: Ananda
authors.affiliation: Canberra and Calvary Hospitals, Department of Medical Oncology, Garran, ACT, Australia.
authors.forename: Desmond
authors.initials: D
authors.lastname: Yip
authors.affiliation: Cabrini Health, Department of Medical Oncology, Malvern, VIC, Australia.
authors.forename: Gary
authors.initials: G
authors.lastname: Richardson
authors.affiliation: Eastern Health, Department of Medical Oncology, Boxhill, TAS, Australia.|Monash University, Department of Medicine, Nursing and Health Sciences, Hobart, TAS, Australia.
authors.forename: Phillip
authors.initials: P
authors.lastname: Parente
authors.affiliation: Eastern Health, Department of Medical Oncology, Boxhill, TAS, Australia.
authors.forename: Lionel
authors.initials: L
authors.lastname: Lim
authors.affiliation: John Fawkner Hospital, Department of Medical Oncology, Coburg, VIC, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Stefanou
authors.affiliation: Royal Brisbane Hospital, Department of Medical Oncology, Brisbane, QLD, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Burge
authors.affiliation: Goulburn Valley Health, Department of Medical Oncology, Shepparton, VIC, Australia.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Iddawela
authors.affiliation: Launceston General Hospital, Department of Medical Oncology, Launceston, TAS, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Power
authors.affiliation: Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.|Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.|Faculty of Medicine, Dentistry & Health Sciences University of Melbourne, Melbourne, VIC, Australia.|Western Health, Department of Medical Oncology, Boxhill, TAS, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068258:Bevacizumab / Q000627:therapeutic use*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000068258:Bevacizumab
keywords: GI perforation rate; anti-VEGF therapy; colorectal cancer; drug safety; primary tumor resection