Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL)

Ann Oncol. 2010 Sep;21(9):1804-1809. doi: 10.1093/annonc/mdq020. Epub 2010 Feb 11.

Abstract

Background: Bevacizumab, the anti-vascular endothelial growth factor agent, provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer. We report the final overall survival (OS) analysis from the phase III AVAiL trial.

Patients and methods: Patients (n = 1043) received cisplatin 80 mg/m(2) and gemcitabine 1250 mg/m(2) for up to six cycles plus bevacizumab 7.5 mg/kg (n = 345), bevacizumab 15 mg/kg (n = 351) or placebo (n = 347) every 3 weeks until progression. Primary end point was progression-free survival (PFS); OS was a secondary end point.

Results: Significant PFS prolongation with bevacizumab compared with placebo was maintained with longer follow-up {hazard ratio (HR) [95% confidence interval (CI)] 0.75 (0.64-0.87), P = 0.0003 and 0.85 (0.73-1.00), P = 0.0456} for the 7.5 and 15 mg/kg groups, respectively. Median OS was >13 months in all treatment groups; nevertheless, OS was not significantly increased with bevacizumab [HR (95% CI) 0.93 (0.78-1.11), P = 0.420 and 1.03 (0.86-1.23), P = 0.761] for the 7.5 and 15 mg/kg groups, respectively, versus placebo. Most patients ( approximately 62%) received multiple lines of poststudy treatment. Updated safety results are consistent with those previously reported.

Conclusions: Final analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin-gemcitabine. The PFS benefit did not translate into a significant OS benefit, possibly due to high use of efficacious second-line therapies.

Trial registration: ClinicalTrials.gov NCT00806923.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Carcinoma, Adenosquamous / drug therapy
  • Carcinoma, Adenosquamous / mortality
  • Carcinoma, Adenosquamous / pathology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Gemcitabine
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Placebos
  • Prognosis
  • Survival Rate

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Placebos
  • Deoxycytidine
  • Bevacizumab
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT00806923