Roxanne Nelson

June 01, 2013

CHICAGO — Adding pazopanib (Votrient, GlaxoSmithKline) to the standard treatment regimen increased progression-free survival in women with advanced ovarian cancer. According to new data, pazopanib given after successful treatment with surgery and chemotherapy extended progression-free survival by an average of 5.6 months, as compared with placebo.

The median time to disease progression in the pazopanib group was 17.9 months, compared with 12.3 months in patients receiving placebo.

"Our findings show that we finally have a drug that can maintain control over ovarian cancer growth achieved through initial treatments," said lead author Andreas du Bois, MD, professor of gynecologic oncology at Kliniken Essen Mitte in Essen, Germany. He presented the results of the study at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO®).

Although 70% of patients initially present with advanced disease, the initial response to treatment is high. With modern therapy, about 70% to 85% of patients are free of the initial tumor, but recurrence is high, explained Dr. du Bois. "So there is a rationale for maintaining this high rate of response."

Thus, if pazopanib is approved for ovarian cancer, a number patients will have an extended period without disease recurrence, and it will delay the need for further chemotherapy, he added. "During this time, the patient keeps control over the disease instead of the disease having control over patient's life."

Dr. Andreas du Bois

Pazopanib has already been approved by the US Food and Drug Administration (FDA) for treatment of kidney cancer and soft tissue sarcoma.

The manufacturer announced that it will be filing an approval application for the new indication of maintenance therapy with pazopanib in ovarian cancer on the basis of this trial.

Currently, there are no maintenance therapies approved for ovarian cancer in the United States. In Europe, bevacizumab (Avastin, Genentech, Inc.) is registered for concurrent use with chemotherapy and subsequently as maintenance therapy; this indication is based on a clinical trial that reported extended progression-free survival with its use.

Data Are Encouraging

Approached by Medscape Medical News for an independent comment, Floor J. Backes, MD, assistant professor of medicine at Ohio State University, Columbus, said: "The data are encouraging right now, and it is a very interesting study. The improvement in progression-free survival of 5 months is a meaningful increase."

Dr. Floor J. Backes

"The interesting part will be when the data are mature, and what the overall survival will be," said Dr. Backes. "The follow-up was relatively short, so certainly there may be changes. I doubt there will be a change in progression-free survival, but we do need to wait for the maturation of the data to see if there is an overall survival benefit."

Study Details

The study reported by Dr. du Bois and colleagues involved 940 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers and who showed no evidence of progression after surgery and 5 or more cycles of platinum-taxane chemotherapy. Most of the patients had stage III/IV disease (91%) at initial diagnosis, and no residual disease after surgery (58%).

Patients were randomly assigned in a ratio of 1:1 to receive 800 mg pazopanib once daily or placebo for up to 24 months. The median time from diagnosis to randomization was 7.1 months in the placebo arm and 7.0 months in the pazopanib arm. The median follow-up was 24 months, and the primary endpoint was progression-free survival by response evaluation criteria in solid tumors (RECIST).

As compared with patients receiving placebo, those in the pazopanib arm had a prolonged progression-free survival (HR = 0.766; P = .0021). The authors found that their sensitivity and subgroup analyses of progression-free survival and the analysis of progression-free survival by Gynecologic Cancer InterGroup (GCIG) criteria were consistent with the primary analysis.

In their first interim analysis for overall survival, the authors observed no difference between the 2 treatment arms. However, the overall survival data are not mature, said Dr. du Bois. "The curves are not meaningful at the moment, follow-up is ongoing, and currently, there is no trend in either direction."

There was a higher incidence of adverse events in the pazopanib arm, and there were serious adverse events (26% vs 11%) vs placebo. The most common events noted were hypertension, diarrhea, nausea, headache, fatigue, and neutropenia.

"Relapses remain all too common for women with advanced ovarian cancer, and 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," commented Carol Aghajanian, MD, ASCO spokesperson and gynecologic cancers expert, in a statement.

"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," said Dr. Aghajanian, who is chief of Gynecologic Medical Oncology Service at Memorial Sloan-Kettering Cancer Center in New York City.

The study was supported by GlaxoSmithKline. Dr. du Bois and several coauthors report relationships with GlaxoSmithKline, as noted in the abstract.

2013 Annual Meeting of the American Society of Clinical Oncology. Abstract LBA5503. Presented June 1, 2013.


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