Pazopanib: First Positive Maintenance Trial

Previous trials of maintenance therapy for patients with ovarian cancer have failed to show improved survival. A study presented at the 2013 American Society of Clinical Oncology Annual Meeting is the first successful phase 3 trial in this setting—targeted therapy pazopanib extended progression-free survival (PFS) in women with ovarian cancer by a median of 5.6 months. Women enrolled in the trial were disease free after initial treatment with surgery and chemotherapy.

“Pazopanib maintenance therapy prolongs the time the patient has control over the disease versus the time the disease controls the patient’s life. Pazopanib might be a valuable option for treatment of stage II to IV ovarian cancer,” stated lead author Andreas Du Bois, MD, PhD, professor of gynecologic oncology at the Kliniken Essen-Mitte in Germany.

Although patients with ovarian cancer typically respond to initial therapy with surgery and chemotherapy, the relapse rate is about 75%. The rationale for maintenance therapy is to keep patients in remission, but studies to date have been disappointing. Given the cost and the added toxicity of maintenance therapy, demonstrating improved survival is important.

Pazopanib is an oral multikinase inhibitor approved by the US Food and Drug Administration for the treatment of renal cell carcinoma and soft tissue sarcoma. Medication toxicities reported in the current trial were class specific to angiogenesis inhibitors: hypertension, elevated liver enzymes, neutropenia, and diarrhea.

Most Patients Had Advanced Disease
The phase 3 multicenter trial enrolled 940 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. Eligibility criteria included patients with stage II to IV disease, but most patients had stage III or IV ovarian cancer. Participants were randomized in a 1:1 ratio to receive 800 mg of pazopanib orally versus placebo for 2 years after standard surgery and chemotherapy.

The median time to disease progression was 17.9 months for the pazopanib group versus 12.3 months for the placebo group, representing a 5.6-month advantage for those on the targeted therapy.

At 24 months, however, no significant difference in overall survival was observed. Longer follow-up is needed to see if there is an overall survival benefit.
“There is currently no standard of care for maintenance therapy. Evidence continues to mount that targeting angiogenesis is important in ovarian cancer. The bottom line from several studies is that targeting angiogenesis is effective in ovarian cancer. These results show that pazopanib extends PFS as maintenance therapy, similar to the results of previous trials of bevacizumab,” said Carol Aghajanian, MD, chief of Gynecologic Medical Oncology Service at Memorial Sloan-Kettering Cancer Center, New York City.

“This large trial shows us that targeting multiple molecular cancer drivers can have a substantial impact on this cancer’s ability to grow,” Aghajanian said. “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.”

Reference
Du Bois A, Floquet A, Weon Kim J, et al. Randomized, double-blind, 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 (AEOC): results of an international Intergroup trial (AGO-OVAR16). J Clin Oncol. 2013;31(suppl):Abstract LBA5503. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.