title: Final results of a phase II study of paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer.
abstract: BACKGROUND
  Efficacy and safety data for combining bevacizumab, gemcitabine, and paclitaxel for locally advanced/metastatic breast cancer are limited.
  
  
  METHODS
  AVALUZ trial evaluates the combination of bevacizumab 10 mg/kg, gemcitabine 2,000 mg/m(2) plus paclitaxel 150 mg/m(2), on days 1 and 15 of each 28-day course in previously untreated HER-2 negative patients.
  
  
  RESULTS
  Median progression-free survival (PES): 12.3 months. The overall response and clinical benefit rate (CR + PR + SD) were 72 % (95 % CI 60.9-82.0 %) and 89 % (95 % CI 80.3-95.3 %), respectively. Median overall survival: 27.4 mo. Baseline circulating tumor cell (CTCs) ≥2 versus CTCs <2 was associated with lower PFS, p = 0.046. Overall response was significantly greater in patients with intense angiotensin type 1 receptor (AGTR1) expression (99 vs. 60 % [p = 0.021]). The most frequent grade 3/4 adverse events were: neutropenia (10 %); febrile neutropenia (1 %); sensory neuropathy (13 %); and asthenia (6 %). Grade 3 adverse events of interest with bevacizumab included bleeding (1 %) and hypertension (4 %). One patient developed cardiac ischemia (1 %).
  
  
  CONCLUSIONS
  Adding bevacizumab to chemotherapy appeared feasible and well tolerated, producing toxicity comparable to other effective combined first-line regimens. Baseline circulating endothelial cells and AGTR1 expression are predictive of PFS and response.
authors.affiliation: Department of Oncology, Hospital Universitario de Valme, Carretera de Cadiz, KM 548, 28007, Sevilla, Spain, jsalvad2002@yahoo.es.
authors.forename: J
authors.initials: J
authors.lastname: Salvador
authors.forename: L
authors.initials: L
authors.lastname: Manso
authors.forename: J
authors.initials: J
authors.lastname: de la Haba
authors.forename: A
authors.initials: A
authors.lastname: Jaen
authors.forename: E
authors.initials: E
authors.lastname: Ciruelos
authors.forename: M C
authors.initials: MC
authors.lastname: de Villena
authors.forename: M
authors.initials: M
authors.lastname: Gil
authors.forename: A
authors.initials: A
authors.lastname: Murias
authors.forename: A
authors.initials: A
authors.lastname: Galan
authors.forename: C
authors.initials: C
authors.lastname: Jara
authors.forename: J
authors.initials: J
authors.lastname: Bayo
authors.forename: J M
authors.initials: JM
authors.lastname: Baena
authors.forename: J
authors.initials: J
authors.lastname: Casal
authors.forename: J R
authors.initials: JR
authors.lastname: Mel
authors.forename: I
authors.initials: I
authors.lastname: Blancas
authors.forename: P
authors.initials: P
authors.lastname: Sanchez Rvira
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D057170:Translational Research, Biomedical; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003841:Deoxycytidine; D017239:Paclitaxel; D044140:Receptor, Angiotensin, Type 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D000093542:Gemcitabine; C544065:AGTR1 protein, human