Women with recurrent ovarian cancer experienced significantly improved survival when they received targeted agent cediranib with chemotherapy and as maintenance therapy after chemotherapy, according to the results of a study presented at the ESMO 2013 Congress of the European Society for Medical Oncology in Amsterdam.
Ovarian cancer has the highest mortality rate of all gynecologic cancers. It is the fifth leading cause of cancer death among U.S. women, with roughly 22,000 new cases and 15,000 deaths predicted for 2012. Treatment for ovarian cancer commonly involves surgery and/or chemotherapy. Outcomes for women diagnosed with advanced disease remain poor, and researchers continue to evaluate new approaches to treatment.
Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Cediranib (also known as AZD2171) is a targeted therapy that blocks a protein known as VEGF. VEGF plays a key role in the development of new blood vessels. Cediranib is a potent oral inhibitor of all 3 VEGF tyrosine kinases (VEGF-1, 2, 3), and thus blocks VEGF signaling, angiogenesis, and tumor cell growth.
ICON6 is an international randomized controlled trial that involved 456 patients with relapsed platinum-sensitive ovarian cancer. This was the first trial to examine the activity of an oral VEGF inhibitor in combination with platinum-based chemotherapy and as maintenance therapy in recurrent ovarian cancer. Patients were randomized to one of three treatment arms:
- Platinum-based chemotherapy plus placebo, followed by placebo maintenance therapy
- Platinum-based chemotherapy plus cediranib, followed by placebo maintenance therapy
- Platinum-based chemotherapy plus cediranib, followed by cediranib maintenance therapy
Women received treatment for 18 months or until disease progression, whichever occurred first. The results were groundbreaking. Cediranib plus platinum-based chemotherapy improved progression-free survival by 30 percent. When cediranib was continued as maintenance therapy, it significantly improved both progression-free and overall survival. Among patients who received cediranib with chemotherapy and as maintenance therapy, median progression-free survival was 11.1 months, compared to 8.7 months among patients who received chemotherapy alone. What’s more, patients who received cediranib maintenance had a median overall survival of 26.3 months compared to 20.3 for those who received chemotherapy alone with no maintenance therapy.
The most common adverse events associated with cediranib were hypertension, fatigue, diarrhea, and nausea, which were controlled with dose reduction or interruption in most cases.
Despite the promising results, the future of cediranib in ovarian cancer is uncertain, as the drug’s manufacturer (AstraZeneca) has ceased development of this drug because it did not reach the endpoint that they require to move forward for licensing.
In spite of this uncertainty, the researchers concluded that cediranib given concurrently with platinum-based chemotherapy improves progression-free survival and when continued as maintenance significantly improves both progression-free and overall survival in women with recurrent ovarian cancer.
Ledermann JA, Perren JG, Raja FA, et al. Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: Results of the ICON6 trial. Presented at the 38th Congress of the European Society for Medical Oncology (ESMO), Amsterdam, Netherlands, September 27-October 1, 2013. Abstract LBA10.