ASCO 2013: Pazopanib Maintenance Therapy Delays Relapse of Advanced Ovarian Cancer
A phase III clinical trial has found that pazopanib (Votrient), an oral multikinase inhibitor, extends disease-free survival by an average of 5.6 months, compared to placebo, in women with advanced ovarian cancer who had initial successful treatment with surgery and chemotherapy. “Our findings show that we finally have a drug that can maintain control over ovarian cancer growth achieved through initial treatments,” the study’s lead author Andreas du Bois, MD, Professor of Gynecologic Oncology at Kliniken Essen Mitte in Essen, Germany, reported at the ASCO 2013 Annual Meeting (Abstract LBA5503).
Most Had Stage III/IV Disease
The 940 participants had histologically confirmed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. Eligibility criteria included stage II to IV disease with no evidence of progression after surgery and five or more cycles of platinum-taxane chemotherapy, but 91% had stage III/IV disease at initial diagnosis, and 58% had no residual disease after surgery.
Patients were randomly assigned to receive pazopanib at 800 mg daily or placebo daily for up to 24 months. The median time from diagnosis to randomization was 7.0 months in the pazopanib group and 7.1 months in the placebo group. Median progression-free survival was 17.9 months in the pazopanib group vs 12.3 months in the placebo group (hazard ratio [HR] = 0.766; 95% CI = 0.64–0.91; P= .0021). Overall survival data are not yet mature.
Class-related Toxicities
Pazopanib is a multikinase inhibitor that acts mainly on VEGF, as well as other receptors involved in angiogenesis. “This large trial shows us that targeting multiple molecular cancer drivers can have a substantial impact on this cancer’s ability to grow, giving our patients significantly longer time before relapse,” noted Carol Aghajanian, MD, Chief of the Gynecologic Medical Oncology Service at Memorial Sloan-Kettering Cancer Center in New York. “This study offers a real-world example of how the precision medicine era of cancer research is paying off in areas where no alternate approved drugs exist.”
Patients in the trial experienced some “class-related toxicities,” Dr. du Bois reported. “About 35% of patients experienced hypertension, which needed treatment,” he said. Other class-related toxicities included elevation of liver function enzymes, diarrhea, and neutropenia.
High Relapse Rate
Despite successful initial treatment with surgery and chemotherapy, about 70% of patients with advanced ovarian cancer experience a relapse, half in the first year. “If pazopanib is approved for ovarian cancer, many patients will experience longer disease-free and chemotherapy-free periods,” Dr. du Bois said.
Pazopanib is already approved by the FDA for treatment of kidney cancer and soft tissue sarcoma. No maintenance therapies are currently approved for ovarian cancer in the United States, although bevacizumab (Avastin) is registered for use concurrently with chemotherapy and subsequently as maintenance therapy in Europe based on a clinical trial reporting extension of progression-free survival.
This research was supported by GlaxoSmithKline. Dr. du Bois reported honoraria from GlaxoSmithKline.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
