Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial

Background: This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). Patients and methods: Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/ kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. Results: In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade >= 2 hypertension and grade >= 3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. Conclusion: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.