Pazopanib Maintenance Therapy Extends Progression‑free Survival in Patients with Ovarian Cancer 


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Maintenance therapy with the targeted therapy pazopanib (Votrient) extended progression-free survival in women with ovarian cancer who were disease-free following initial treatment with surgery and chemotherapy, according to results of a phase III trial presented at the 49th Annual Meeting of ASCO.1 Women on the maintenance therapy arm lived about 5.6 months longer than those on placebo.

This is the first positive phase III trial in the pure maintenance setting—ie, maintenance therapy was initiated 7 months after diagnosis and after completion of primary treatment—to demonstrate superior outcome for a targeted therapy. Other trials have shown that bevacizumab (Avastin) given as initial therapy and continued through maintenance improves progression-free survival.2

No Overall Survival Trend

“[Maintenance therapy with] pazopanib prolongs the time the patient has control over the disease vs the time the disease controls the patient’s life. Overall survival data are immature, and so far there is no survival trend in either direction. Pazopanib might be a valuable option for treatment of stage II–IV ovarian cancer,” stated lead author Andreas du Bois, MD, Professor of Gynecologic Oncology at Kliniken Essen Mitte in Essen, Germany. Dr. du Bois said toxicities of pazopanib are class-specific to angiogenesis inhibitors: hypertension, elevated liver enzymes, neutropenia, and diarrhea.

Ovarian cancer has the highest mortality among all gynecologic cancers. Seventy percent of women have advanced disease at the time of diagnosis. Although patients respond to initial therapy with surgery and chemotherapy, about 75% of patients will relapse, providing a rationale for maintenance therapy to maintain response, Dr. du Bois explained.

Pazopanib is an oral, multitargeted kinase inhibitor that binds to VEGFR, PDGFR, and several other proteins involved in angiogenesis, tumor proliferation, and cell survival. The drug is approved by the U.S. Food and Drug Administration for the treatment of patients with renal cancer and soft-tissue sarcoma.

Study Background

The phase III multicenter trial included 940 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer randomly assigned in a 1:1 ratio to receive pazopanib orally for 2 years vs placebo. Patients had stage II to IV ovarian cancer and were treated successfully with standard therapy (surgery and five or more cycles of chemotherapy). After a 7-month disease-free interval, they were randomly assigned to the study arms.

“Keep that extra 7 months in mind when we look at the [not yet mature] survival data, which was evaluated from time of randomization,” he noted.

For the primary endpoint of progression-free survival, median time to progression from randomization was 17.9 months for the pazopanib group vs 12.3 months for placebo, representing a 5.6-month advantage for those on the targeted therapy, for a 24% reduction in risk of recurrence or death. At a median follow-up of 24.3 months, no significant difference in overall survival was observed. ■

Disclosure: Dr. du Bois reported no potential conflicts of interest.

References

1. Du Bois A, Floquet A, Kim JW, et al: Randomized, double-blind placebo, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: Results of an international Intergroup trial (AGO-OVAR16). ASCO Annual Meeting. Abstract LBA5503. Presented June 2, 2013.

2. Perren TJ, Swart AM, Pfisterer J, et al: A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365:2484-2496, 2011.


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