Randomized, Double-Blind Trial of Carboplatin and Paclitaxel With Either Daily Oral Cediranib or Placebo in Advanced Non–Small-Cell Lung Cancer: NCIC Clinical Trials Group BR24 Study Journal Articles uri icon

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  • Purpose This phase II/III double-blind study assessed efficacy and safety of cediranib with standard chemotherapy as initial therapy for advanced non–small-cell lung cancer (NSCLC). Patients and Methods Paclitaxel (200 mg/m2) and carboplatin (area under the serum concentration-time curve 6) were given every 3 weeks, with daily oral cediranib or placebo at 30 mg (first 45 patients received 45 mg). Progression-free survival (PFS) was the primary outcome of the phase II interim analysis; phase III would proceed if the hazard ratio (HR) for PFS ≤ 0.77 and toxicity were acceptable. Results A total of 296 patients were enrolled, 251 to the 30-mg cohort. The phase II interim analysis demonstrated a significantly higher response rate (RR) for cediranib than for placebo, HR of 0.77 for PFS, no excess hemoptysis, and a similar number of deaths in each arm. The study was halted to review imbalances in assigned causes of death. In the primary phase II analysis (30-mg cohort), the adjusted HR for PFS was 0.77 (95% CI, 0.56 to 1.08) with a higher RR for cediranib than for placebo (38% v 16%; P < .0001). Cediranib patients had more hypertension, hypothyroidism, hand-foot syndrome, and GI toxicity. Hypoalbuminemia, age ≥ 65 years, and female sex predicted increased toxicity. Survival update (N = 296) 10 months after study unblinding favored cediranib over placebo (median of 10.5 months v 10.1 months; HR, 0.78; 95% CI, 0.57 to 1.06; P = .11). Causes of death in the cediranib 30-mg cohort were NSCLC (81%), protocol toxicity ± NSCLC (13%), and other (6%); for the placebo group, they were 98%, 0%, and 2%, respectively. Conclusion The addition of cediranib to carboplatin/paclitaxel results in improved response and PFS, but does not appear tolerable at a 30-mg dose. Consequently, the National Cancer Institute of Canada Clinical Trials Group and the Australasian Lung Cancer Trials Group initiated a randomized, double-blind, placebo-controlled trial of cediranib 20 mg with carboplatin and paclitaxel in advanced NSCLC.


  • Goss, Glenwood D
  • Arnold, Andrew
  • Shepherd, Frances A
  • Dediu, Mircea
  • Ciuleanu, Tudor-Eliade
  • Fenton, David
  • Zukin, Mauro
  • Walde, David
  • Laberge, Francis
  • Vincent, Mark D
  • Ellis, Peter
  • Laurie, Scott A
  • Ding, Keyue
  • Frymire, Eliot
  • Gauthier, Isabelle
  • Leighl, Natasha B
  • Ho, Cheryl
  • Noble, Jonathan
  • Lee, Christopher W
  • Seymour, Lesley

publication date

  • January 1, 2010

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