title: Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06).
abstract: BACKGROUND
  Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy.
  
  
  METHODS
  In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%.
  
  
  RESULTS
  The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient.
  
  
  CONCLUSIONS
  Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy.
  
  
  BACKGROUND
  ClinicalTrials.gov, number NCT00544700.
authors.affiliation: Department of Oncology, Kantonsspital St Gallen, St Gallen. Electronic address: dieter.koeberle@claraspital.ch.
authors.forename: D
authors.initials: D
authors.lastname: Koeberle
authors.affiliation: Department of Oncology, Hôpital Fribourgeois, Fribourg.
authors.forename: D C
authors.initials: DC
authors.lastname: Betticher
authors.affiliation: Department of Oncology, Kantonsspital Chur, Chur.
authors.forename: R
authors.initials: R
authors.lastname: von Moos
authors.affiliation: SAKK Coordinating Centre, Bern.
authors.forename: D
authors.initials: D
authors.lastname: Dietrich
authors.affiliation: SAKK Coordinating Centre, Bern.
authors.forename: P
authors.initials: P
authors.lastname: Brauchli
authors.affiliation: SAKK Coordinating Centre, Bern.
authors.forename: D
authors.initials: D
authors.lastname: Baertschi
authors.affiliation: Institute of Pharmaceutical Medicine/ECPM, Basel.
authors.forename: K
authors.initials: K
authors.lastname: Matter
authors.affiliation: Department of Oncology, Kantonsspital Luzern, Luzern.
authors.forename: R
authors.initials: R
authors.lastname: Winterhalder
authors.affiliation: Department of Oncology, Spitalzentrum Biel, Biel.
authors.forename: M
authors.initials: M
authors.lastname: Borner
authors.affiliation: Department of Oncology, Hôpital de Sion, Sion.
authors.forename: S
authors.initials: S
authors.lastname: Anchisi
authors.affiliation: Department of Oncology, Kantonsspital Aarau, Aarau.
authors.forename: P
authors.initials: P
authors.lastname: Moosmann
authors.affiliation: Department of Oncology, Inselspital Bern, Bern.
authors.forename: A
authors.initials: A
authors.lastname: Kollar
authors.affiliation: Department of Oncology, IOSI, Bellinzona.
authors.forename: P
authors.initials: P
authors.lastname: Saletti
authors.affiliation: Department of Oncology, HCUG, Geneva.
authors.forename: A
authors.initials: A
authors.lastname: Roth
authors.affiliation: Department of Oncology, Kantonsspital St Gallen, St Gallen.
authors.forename: M
authors.initials: M
authors.lastname: Frueh
authors.affiliation: Department of Oncology, Hôpital Fribourgeois, Fribourg.
authors.forename: M
authors.initials: M
authors.lastname: Kueng
authors.affiliation: Department of Oncology, Hirslanden Klinik Aarau, Aarau.
authors.forename: R A
authors.initials: RA
authors.lastname: Popescu
authors.affiliation: Department of Oncology, Kantonsspital Winterthur, Winterthur.
authors.forename: S
authors.initials: S
authors.lastname: Schacher
authors.affiliation: Department of Oncology, Universitätsspital Basel, Basel, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Hess
authors.affiliation: Department of Oncology, Universitätsspital Basel, Basel, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Herrmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: bevacizumab; maintenance therapy; metastatic colorectal cancer