title: First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: safety and efficacy in an open-label study in 2,251 patients.
abstract: BACKGROUND
  First-line bevacizumab combined with chemotherapy significantly improves efficacy versus chemotherapy alone in human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer (LR/mBC). This large, open-label study further assesses first-line bevacizumab with taxane-based chemotherapy in routine oncology practice.
  
  
  METHODS
  Patients with HER2-negative LR/mBC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of zero to two and no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks plus taxane-based chemotherapy (or other non-anthracycline chemotherapy) until disease progression, unacceptable toxicity or patient withdrawal. The primary end point was safety; time to progression (TtP) was a secondary end point.
  
  
  RESULTS
  Median follow-up in 2251 treated patients was 12.7 months. Median age was 53 years and 94% of patients had ECOG PS of zero or one. Bevacizumab was most commonly administered with single-agent paclitaxel (35%), single-agent docetaxel (33%) or taxane-based combination therapy (10%). The most frequent grade ≥3 adverse event (AE) was neutropenia (5.4%). Grade ≥3 AEs previously associated with bevacizumab included hypertension (4.4%), arterial/venous thromboembolism (3.2%), proteinuria (1.7%) and bleeding (1.4%). No new bevacizumab safety signals were observed. Median TtP was 9.5 months (95% confidence interval 9.1-9.9).
  
  
  CONCLUSIONS
  The study population in ATHENA was more representative of general oncology practice than populations enrolled into randomised trials, although there may have been some bias towards younger, fitter patients. The safety and efficacy of bevacizumab-taxane therapy in this large study were consistent with results from randomised first-line trials.
authors.affiliation: Breast Unit, Royal Marsden Hospital, London, and the Institute of Cancer Research, London, UK. Electronic address: ian.smith@rmh.nhs.uk.
authors.forename: I E
authors.initials: IE
authors.lastname: Smith
authors.affiliation: Department of Medical Oncology, Institut Curie, Université Paris Descartes, Paris, France.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Pierga
authors.affiliation: Medical Oncology Unit, Department of Oncology, Prato Hospital, Tuscany Cancer Institute, Prato, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Biganzoli
authors.affiliation: Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Cortés-Funes
authors.affiliation: Department of Gynaecology, Martin-Luther-Universitaet Halle-Wittenberg, Halle, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Thomssen
authors.affiliation: Department of Medical Oncology, University Hospital Jean Minjoz, Besançon, France.
authors.forename: X
authors.initials: X
authors.lastname: Pivot
authors.affiliation: Division of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Fabi
authors.affiliation: Department of Medical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Xu
authors.affiliation: Chemotherapeutic Department, City Clinical Oncology Hospital #62, Moscow, Russia.
authors.forename: D
authors.initials: D
authors.lastname: Stroyakovskiy
authors.affiliation: Cancer Treatment Centre (CACON), Associação Hospital de Caridade de Ijuí, Ijuí, Brazil.
authors.forename: F A
authors.initials: FA
authors.lastname: Franke
authors.affiliation: Breast Cancer Unit, Sheba Tel Hashomer, Ramat Gan, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Kaufman
authors.affiliation: Department of Cancer Services, Mater Hospital, South Brisbane, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Mainwaring
authors.affiliation: Department of Breast Cancer and Reconstructive Surgery, Marii Sklodowskiej-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Pienkowski
authors.affiliation: Department of Haematology/Medical Oncology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: De Valk
authors.affiliation: Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: A
authors.initials: A
authors.lastname: Kwong
authors.affiliation: Department of Medical Oncology, Fundación Rodolfo Padilla, Padilla, Mexico.
authors.forename: J L
authors.initials: JL
authors.lastname: González-Trujillo
authors.affiliation: Department of Medical Oncology, National Cancer Institute, Bratislava, Slovak Republic.
authors.forename: I
authors.initials: I
authors.lastname: Koza
authors.affiliation: Department of Medical Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Petrakova
authors.affiliation: Medical Oncology Department, Instituto Português de Oncologia do Porto Francisco Gentil, Porto, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Pereira
authors.affiliation: Sunnybrook Odette Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: K I
authors.initials: KI
authors.lastname: Pritchard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001952:Bridged-Ring Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; C080625:taxane; C508053:ERBB2 protein, human