Pazopanib Improves Progression-Free Survival for Advanced Ovarian Cancer

Chicago—Patients with advanced ovarian cancer who took pazopanib daily after initial treatment with surgery and chemotherapy had significantly longer progression-free survival compared with those who received placebo, according to results of a randomized, double-blind, phase 3 trial. The median progression-free survival from randomization was 17.9 months in the pazopanib group and 12.3 months in the placebo group (hazard ratio, 0.766; P=.0021).

Andreas du Bois, MD, the study’s lead author, presented the data in a late-breaking oral abstract session at the ASCO meeting. GlaxoSmithKline, the drug’s marketer, supported the study.

Dr. du Bois said this was the first positive phase 3 trial for maintenance therapy with targeted agents in ovarian cancer. He added that data were “not very meaningful at the moment” since only 20% of patients (n=190) had died during an interim analysis, which found overall survival was similar between the groups. The final overall survival analysis will occur after 551 patients have died.

“There is not any conclusion we can draw from [the overall survival data], only that there is no early detrimental effect,” Dr. du Bois said.

Pazopanib, an oral, multi-target tyrosine kinase inhibitor, is FDA approved to treat patients with advanced renal cell carcinoma and advanced soft tissue sarcoma who have received prior chemotherapy. In the United States, no maintenance therapies are approved to treat ovarian cancer.

When diagnosed with ovarian cancer, approximately 70% of patients will have advanced disease, according to Dr. du Bois, who added that ovarian cancer has the highest mortality risk among all gynecological tumors. Dr. du Bois said initial therapy for ovarian cancer has become “better and better” in recent years. Most patients start treatment with surgery and chemotherapy, and 70% to 85% are tumor-free after initial therapy. However, nearly 75% of patients will relapse.

From June 2009 to August 2010, the authors randomized 940 patients with advanced ovarian cancer in a 1:1 ratio to receive 800 mg of pazopanib or placebo daily for up to 24 months. Patients entered the study after completing their initial treatment with surgery and chemotherapy. There was a median of 7 months from diagnosis to randomization. The median time from last chemotherapy treatment to entering the trial was 8 weeks.

The median age of patients was 57 years, and 77% had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0. Patients were excluded if they needed imminent second-line treatment and had received prior anti-vascular endothelial growth factor therapy.

The authors also performed pre-specified subgroup analyses based on age, ECOG status, tumor stage, and other groups. Dr. du Bois said the results were “very robust” and showed a significant advantage of pazopanib over placebo in terms of progression-free survival.

The following serious adverse events were more common in patients taking pazopanib: hypertension, liver-related toxicity, neutropenia, and diarrhea. Dr. du Bois noted that 17% of patients in the placebo group and 52% of patients in the pazopanib group had hypertension and required treatment with a drug. By the end of the study, >50% of patients had a dose reduction.

Dr. du Bois said studies are being planned to predict tolerability of pazopanib for patients with advanced ovarian cancer. He added that patients should be aware of the toxicities, and healthcare professionals should better understand how to manage the adverse events.