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.
Author(s): Goss GD, Arnold A, Shepherd FA, Dediu M, Ciuleanu TE, Fenton D, Zukin M, Walde D,
Laberge F, Vincent MD, Ellis PM, Laurie SA, Ding K, Frymire E, Gauthier I, Leighl
NB, Ho C, Noble J, Lee CW, Seymour L.
Affiliation(s): FCP(SA), FRCPC, The Ottawa Hospital Cancer Centre, 501 Smyth Rd, Ottawa ON K1H
8L6, Canada. ggoss@ottawahospital.on.ca
Publication date & source: 2010, J Clin Oncol. , 28(1):49-55
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/m(2))
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 < or = 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 > or = 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.
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