title: Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.
abstract: OBJECTIVE
  Treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the rationale for a phase III trial of gemcitabine-erlotinib plus bevacizumab or placebo.
  
  
  METHODS
  Patients with metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine (1,000 mg/m(2)/week), erlotinib (100 mg/day), and bevacizumab (5 mg/kg every 2 weeks) or gemcitabine, erlotinib, and placebo in this double-blind, phase III trial. Primary end point was OS; secondary end points included progression-free survival (PFS), disease control rate, and safety.
  
  
  RESULTS
  A total of 301 patients were randomly assigned to the placebo group and 306 to the bevacizumab group. Median OS was 7.1 and 6.0 months in the bevacizumab and placebo arms, respectively (hazard ratio [HR], 0.89; 95% CI, 0.74 to 1.07; P = .2087); this difference was not statistically significant. Adding bevacizumab to gemcitabine-erlotinib significantly improved PFS (HR, 0.73; 95% CI, 0.61 to 0.86; P = .0002). Treatment with bevacizumab plus gemcitabine-erlotinib was well tolerated: safety data did not differ from previously described safety profiles for individual drugs.
  
  
  CONCLUSIONS
  The primary objective was not met. The addition of bevacizumab to gemcitabine-erlotinib did not lead to a statistically significant improvement in OS in patients with metastatic pancreatic cancer. PFS, however, was significantly longer in the bevacizumab group compared with placebo. No unexpected safety events were observed from adding bevacizumab to gemcitabine-erlotinib.
authors.affiliation: University Hospital Gasthuisberg/Leuven, Digestive Oncology Unit, Herestraat 49, B-3000 Leuven, Belgium. eric.vancutsem@uz.kuleuven.ac.be
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Walter L
authors.initials: WL
authors.lastname: Vervenne
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
authors.forename: Yves
authors.initials: Y
authors.lastname: Humblet
authors.forename: Sharlene
authors.initials: S
authors.lastname: Gill
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Van Laethem
authors.forename: Chris
authors.initials: C
authors.lastname: Verslype
authors.forename: Werner
authors.initials: W
authors.lastname: Scheithauer
authors.forename: Aijing
authors.initials: A
authors.lastname: Shang
authors.forename: Jan
authors.initials: J
authors.lastname: Cosaert
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069347:Erlotinib Hydrochloride; D006801:Humans; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine