title: Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer.
abstract: The randomised phase III TANIA trial demonstrated that continuing bevacizumab with second-line chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC) after progression on first-line bevacizumab-containing therapy significantly improved progression-free survival (PFS) compared with chemotherapy alone [hazard ratio (HR) = 0.75, 95% confidence interval (CI) 0.61-0.93]. We report final results from the TANIA trial, including overall survival (OS) and health-related quality of life (HRQoL).
  
  
  
  Patients with HER2-negative LR/mBC that had progressed on or after first-line bevacizumab plus chemotherapy were randomised to receive standard second-line chemotherapy either alone or with bevacizumab. At second progression, patients initially randomised to bevacizumab continued bevacizumab with their third-line chemotherapy, but those randomised to chemotherapy alone were not allowed to cross over to receive third-line bevacizumab. The primary end point was second-line PFS; secondary end points included third-line PFS, combined second- and third-line PFS, OS, HRQoL and safety.
  
  
  
  Of the 494 patients randomised, 483 received second-line therapy; 234 patients (47% of the randomised population) continued to third-line study treatment. The median duration of follow-up at the final analysis was 32.1 months in the chemotherapy-alone arm and 30.9 months in the bevacizumab plus chemotherapy arm. There was no statistically significant difference between treatment arms in third-line PFS (HR = 0.79, 95% CI 0.59-1.06), combined second- and third-line PFS (HR = 0.85, 95% CI 0.68-1.05) or OS (HR = 0.96, 95% CI 0.76-1.21). Third-line safety results showed increased incidences of proteinuria and hypertension with bevacizumab, consistent with safety results for the second-line treatment phase. No differences in HRQoL were detected.
  
  
  
  In this trial, continuing bevacizumab beyond first and second progression of LR/mBC improved second-line PFS, but no improvement in longer term efficacy was observed. The second-line PFS benefit appears to be achieved without detrimentally affecting quality of life.
  
  
  
  NCT01250379.
authors: Department of Oncology, University Hospital Split, Split, Croatia edo.vrdoljak@gmail.com.
authors: E
authors: E
authors: Vrdoljak
authors: Outpatient Cancer Center, Freiburg, Germany.
authors: N
authors: N
authors: Marschner
authors: Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria.|Central European Cooperative Oncology Group (CECOG).
authors: C
authors: C
authors: Zielinski
authors: Assistance Publique Hôpitaux de Paris-Tenon, IUC-UPMC, Sorbonne University, Paris, France.
authors: J
authors: J
authors: Gligorov
authors: Ramon y Cajal University Hospital, Madrid.|Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors: J
authors: J
authors: Cortes
authors: Department of Medical and Biological Sciences, University of Udine, Udine.|Department of Oncology, University Hospital of Udine, Udine, Italy.
authors: F
authors: F
authors: Puglisi
authors: Multidisciplinary Institute of Oncology, Clinique de Genolier, Genolier, Switzerland.
authors: M
authors: M
authors: Aapro
authors: Sussex Health Outcomes Research and Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Falmer, UK.
authors: L
authors: L
authors: Fallowfield
authors: Medical Oncology Unit 2, Pisa Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy.
authors: A
authors: A
authors: Fontana
authors: Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: M
authors: M
authors: Inbar
authors: Department of Oncotherapy, University of Szeged, Szeged, Hungary.
authors: Z
authors: Z
authors: Kahan
authors: West German Cancer Center, University Duisburg-Essen, Essen.|German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany.
authors: A
authors: A
authors: Welt
authors: Oncology Department, Centre François Baclesse, Caen.
authors: C
authors: C
authors: Lévy
authors: Institut Curie-Hôpital René Huguenin, Saint-Cloud.
authors: E
authors: E
authors: Brain
authors: Oncology Department, Jean Minjoz University Hospital, Besançon, France.
authors: X
authors: X
authors: Pivot
authors: Oncology Unit, University Hospital of Sassari, Sassari, Italy.
authors: C
authors: C
authors: Putzu
authors: MD Anderson Cancer Center Spain, Madrid, Spain.
authors: A
authors: A
authors: González Martín
authors: F Hoffmann-La Roche Ltd, Basel.
authors: S
authors: S
authors: de Ducla
authors: Stamford Consultants AG, on behalf of F Hoffmann-La Roche Ltd, Basel, Switzerland.
authors: V
authors: V
authors: Easton
authors: German Breast Group, Neu-Isenburg, Germany.
authors: G
authors: G
authors: von Minckwitz
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011788:Quality of Life; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: antiangiogenesis; bevacizumab; metastatic breast cancer; quality of life; retreatment