Despite previously reported progression-free survival improvements with cediranib, results from the ICON6 trial failed to show a statistically significant improvement in overall survival.
Despite previously reported improvements in progression-free survival (PFS) associated with the investigational oral vascular endothelial growth factor receptor (VEGFR)-2 inhibitor cediranib (AZD 2171), cediranib was not associated with a statistically significant improvement in overall survival (OS) in women with platinum-sensitive relapsed ovarian cancer, according to results of an analysis of mature long-term survival data from the ICON6 trial, presented (abstract 5506) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.
The study was “unavoidably underpowered” for assessing survival outcomes because of low accrual. Nevertheless, the numeric median difference in OS time was 7.4 months, with the deaths of 85% of patients having been reported, noted lead study author Jonathan A. Ledermann, MD, of the University College London Cancer Institute in England.
The study authors had enrolled women with epithelial ovarian, fallopian tube, or serous primary peritoneal cancer who experienced computed tomography (CT)- or magnetic resonance imaging (MRI)-confirmed relapse more than 6 months after primary chemotherapy. Patients with a performance status of 0 or 1 deemed able to undergo platinum-based chemotherapy were included; those with uncontrolled hypertension, arterial thrombosis or hemorrhage, or recent surgery were not eligible.
The study involved a safety stage, an activity stage (with PFS and OS outcomes), and an efficacy stage (OS). However, in October of 2011, with 440 patients enrolled out of 2,000 planned for the efficacy stage, AstraZeneca discontinued cediranib development, and the authors revised the study design, making PFS the primary endpoint and OS and toxicity secondary endpoints for the efficacy stage.
As previously reported, PFS was 8.7 months in the placebo arm vs 11.1 months for patients receiving cediranib (hazard ratio [HR], 0.57; 95% CI, 0.45–0.74; P = .00001), Dr. Ledermann said.
However, at a median follow-up of 25.6 months, the newly reported OS results for chemotherapy with concurrent and maintenance cediranib were not significantly better than the results for chemotherapy and placebo (median OS, 27.3 vs 19.9 months; P = .21). Maintenance therapy with chemotherapy and cediranib was associated with a median time from diagnosis to death of 51.3 months, compared with 43.3 months for chemotherapy and placebo.
Cediranib maintenance therapy is undergoing further study in ICON9, Dr. Ledermann said.