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

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)

M Reck  1 , J von Pawel  2 , P Zatloukal  3 , R Ramlau  4 , V Gorbounova  5 , V Hirsh  6 , N Leighl  7 , J Mezger  8 , V Archer  9 , N Moore  10 , C Manegold  11 ; BO17704 Study Group
Affiliations
Clinical Trial

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)

M Reck et al. Ann Oncol. 2010 Sep.

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.

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Figures

Figure 1.
Figure 1.
Plots of Kaplan–Meier estimates for OS (ITT population) for the bevacizumab 7.5 mg/kg group and the bevacizumab 15 mg/kg group relative to placebo, together with time to event data for the OS analysis in the ITT and PP populations (A) and for the subgroup of patients who did not receive poststudy therapy (B). In panel b, data from the two bevacizumab groups have been pooled. CG, cisplatin–gemcitabine; CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; PP, per protocol.
Figure 2.
Figure 2.
Forest plots of HRs for OS by subgroup for each bevacizumab group relative to placebo (ITT population). CG, cisplatin–gemcitabine; ECOG, Eastern Cooperative Oncology Group.
See this image and copyright information in PMC

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