A multikinase inhibitor delays relapse in advanced disease
August 2013 Vol 6, No 6 Special Issue - Emerging Therapies
Phoebe Starr

Chicago, IL—Previous trials of maintenance therapy for patients with ovarian cancer have failed to show improved survival. A study presented at ASCO 2013 is the first successful phase 3 trial in this setting, showing that the targeted therapy pazopanib (Votrient) extended progression-free survival (PFS) by a median of 5.6 months in women with ovarian cancer. Women who were enrolled in the trial were free of the disease after the 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 stages II to IV ovarian cancer,” stated lead investigator Andreas Du Bois, MD, Director, Department of Gynecology and Gy­necologic Oncology, at Kliniken Essen Mitte, Germany.

Although patients with ovarian cancer typically respond to initial therapy with surgery and chemotherapy, the relapse rate for this type of cancer is approximately 75%. The rationale for maintenance therapy is to keep patients in remission, but results of studies to date have been disappointing. Given the cost and the added toxicity of maintenance therapy, demonstrating improved survival with an agent is important for its approval.
Pazopanib is an oral multikinase inhibitor that is approved by the US Food and Drug Administration for the treatment of renal-cell carcinoma and soft-tissue sarcoma.

Medication side effects reported in the current trial were class-specific to angiogenesis inhibitors: hypertension, elevated liver enzymes, neutropenia, and diarrhea.

Most Patients Had Advanced Disease
This phase 3 multicenter trial included 940 patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers. Trial eligibility criteria included 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 once daily or placebo for up to 2 years after standard surgery and chemotherapy.

The median time to disease progression was 17.9 months for the paz­opanib group compared with 12.3 months for the placebo group, representing a 5.6-month advantage for patients receiving the targeted therapy, for a 24% reduction in the risk of recurrence or of death.

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, Gynecologic Medical Oncology Service, Memorial Sloan-Kettering Cancer Center, New York.

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

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August 2013 Vol 6, No 6 Special Issue published on August 22, 2013 in Personalized Medicine
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