title: Final efficacy and updated safety results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer.
abstract: BACKGROUND
  The purpose of this analysis was to assess the long-term impact of adding bevacizumab to adjuvant chemotherapy for early triple-negative breast cancer (TNBC).
  
  
  METHODS
  Patients eligible for the open-label randomized phase III BEATRICE trial had centrally confirmed triple-negative operable primary invasive breast cancer (pT1a-pT3). Investigators selected anthracycline- and/or taxane-based chemotherapy for each patient. After definitive surgery, patients were randomized 1:1 to receive ≥4 cycles of chemotherapy alone or with 1 year of bevacizumab (5 mg/kg/week equivalent). Stratification factors were nodal status, selected chemotherapy, hormone receptor status, and type of surgery. The primary end point was invasive disease-free survival (IDFS; previously reported). Secondary outcome measures included overall survival (OS) and safety.
  
  
  RESULTS
  After 56 months' median follow-up, 293 of 2591 randomized patients had died. There was no statistically significant difference in OS between treatment arms in either the total population (hazard ratio 0.93, 95% confidence interval [CI] 0.74-1.17; P = 0.52) or pre-specified subgroups. The 5-year OS rate was 88% (95% CI 86-90%) in both treatment arms. Updated IDFS results were consistent with the primary IDFS analysis. Five-year IDFS rates were 77% (95% CI 75-79%) with chemotherapy alone versus 80% (95% CI 77-82%) with bevacizumab. From 18 months after first study dose to study end, new grade ≥3 adverse events occurred in 4.6% and 4.5% of patients in the two arms, respectively.
  
  
  CONCLUSIONS
  Final OS results showed no significant benefit from bevacizumab therapy for early TNBC. Late-onset toxicities were rare in both groups. Five-year OS and IDFS rates suggest that the prognosis for patients with TNBC is better than previously thought.
  
  
  BACKGROUND
  NCT00528567.
authors.affiliation: Faculty of Medicine, Deakin University, Geelong, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Bell
authors.affiliation: Clinical Trials Research Unit, University of Leeds, Leeds.
authors.forename: J
authors.initials: J
authors.lastname: Brown
authors.affiliation: Medical Research Council Clinical Trials Unit, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Parmar
authors.affiliation: Faculty of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Toi
authors.affiliation: Swiss Cardiovascular Center, Bern University Hospital, Bern, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Suter
authors.affiliation: Department of Internal Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: G G
authors.initials: GG
authors.lastname: Steger
authors.affiliation: Medical Oncology Service, University Hospital Jean Minjoz, Besançon, France.
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authors.lastname: Pivot
authors.affiliation: Medical Oncology, Cross Center Institute, Edmonton, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Mackey
authors.affiliation: Department of Obstetrics and Gynecology and Breast Cancer Center, Sana Klinikum Offenbach, Offenbach, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Jackisch
authors.affiliation: Department of Medical Oncology, National Cancer Center, Singapore, Singapore, and Sunnybrook Health Sciences Center, University of Toronto, Toronto, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Dent
authors.affiliation: Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.
authors.forename: P
authors.initials: P
authors.lastname: Hall
authors.affiliation: Product Development Oncology, F Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Xu
authors.affiliation: Product Development Oncology, F Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Morales
authors.affiliation: Centre des Maladies du Sein Deschênes-Fabia, CHU de Québec-Hôpital du Saint-Sacrement, Ville de Québec, Québec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Provencher
authors.affiliation: Oncology Department, Perola Byington Hospital/FMUSP, São Paulo, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Hegg
authors.affiliation: Department of Medical Oncology, Centre Oscar Lambret, Lille, France.
authors.forename: L
authors.initials: L
authors.lastname: Vanlemmens
authors.affiliation: Onkologischer Schwerpunktam Oskar-Helene-Heim, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kirsch
authors.affiliation: Division of Gynecologic Oncology, National Center for Tumor Diseases, University Hospital, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schneeweiss
authors.affiliation: Department of Surgery, Breast Oncology NHO Osaka National Hospital, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Oncologianova, Recklinghausen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Overkamp
authors.affiliation: Edinburgh University Cancer Research Centre, University of Edinburgh and Cancer Services, NHS Lothian, Edinburgh, UK.
authors.forename: D
authors.initials: D
authors.lastname: Cameron
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000068258:Bevacizumab
keywords: bevacizumab; breast cancer; chemotherapy; survival; triple negative