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†

Ann Oncol. 2015 May;26(5):908-14. doi: 10.1093/annonc/mdv065. Epub 2015 Feb 16.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00930891.

Keywords: anti-angiogenesis therapy; bevacizumab; chemotherapy; small-cell lung cancer.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / adverse effects
  • Bevacizumab / therapeutic use*
  • Cisplatin / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Disease-Free Survival
  • Epirubicin / therapeutic use
  • Etoposide / therapeutic use
  • Female
  • France
  • Humans
  • Induction Chemotherapy
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Bevacizumab
  • Epirubicin
  • Etoposide
  • Cyclophosphamide
  • Cisplatin

Associated data

  • ClinicalTrials.gov/NCT00930891