Adding Cediranib to Platinum Therapy Increases Progression-Free Survival in Relapsed Platinum-Sensitive Ovarian Cancer
The phase III ICON6 trial showed that adding cediranib to platinum-based therapy increased progression-free survival and toxicity in women with first relapse of platinum-sensitive ovarian cancer, reported Ledermann et al in The Lancet.
Study Details
In the double-blind trial, 456 women with relapse of platinum-sensitive ovarian cancer from 63 sites in Australia, Canada, New Zealand, Spain, and the UK were randomized 2:3:3 between November 2007 and December 2011 to receive up to six cycles of platinum-based chemotherapy with placebo and then placebo maintenance (n = 118), chemotherapy plus cediranib at 20 mg once daily and then placebo maintenance (n = 174), or chemotherapy plus cediranib and then cediranib at 20 mg once daily maintenance (n = 164).
Treatment was continued until disease progression or excessive toxicity. An initial 30 patients randomized to a 30-mg cediranib dose were excluded due to excessive toxicity. The primary endpoint was progression-free survival for the placebo/placebo maintenance group vs the cediranib/cediranib maintenance group.
Progression-Free Survival
Median follow-up was 19.5 months. Median progression-free survival was 11.0 months (95% confidence interval [CI] = 10.4–11.7 months) in the cediranib/cediranib maintenance group vs 8.7 months (95% CI = 7.7–9.4 months) in the placebo/placebo maintenance group (hazard ratio = 0.56, P < .0001). Median progression-free survival in the cediranib/placebo maintenance group was 9.9 months (95% CI = 9.4–10.5 moths).
Toxicity
During the chemotherapy phase, adverse events of any grade that were more common in patients receiving vs not receiving cediranib included diarrhea (86% vs 57%), neutropenia (69% vs 47%), hypertension (57% vs 36%), and voice changes (23% vs 6%). During maintenance, diarrhea (92% vs 55%), hypothyroidism (25% vs 9%), and voice changes (25% vs 7%) were more common in patients receiving vs not receiving cediranib maintenance.
Study drug discontinuation due to adverse events was more common in the two groups receiving cediranib during the chemotherapy phase (23% and 27%) vs the chemotherapy-alone group (7%) and was more common during cediranib maintenance (20%) vs the two groups receiving placebo maintenance (5% and 7%).
The investigators concluded: “Cediranib, when given orally with chemotherapy and continued as maintenance, yielded a meaningful [improvement] in progression-free survival in women with recurrent platinum-sensitive ovarian cancer, albeit with added toxic effects. The positive results in ICON6 could provide women with a new therapeutic option for recurrent ovarian cancer. Assessment of the secondary endpoint of overall survival will need longer follow-up.”
The study was funded by the Medical Research Council, Cancer Research UK, the Canadian Cancer Society Research Institute, Cancer Australia, National Gynecological Cancer Centre, and AstraZeneca.
Jonathan A. Ledermann, MD, of the University College London Cancer Institute, is the corresponding author of The Lancet article.
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