CHICAGO—Maintenance therapy with pazopanib after successful initial chemotherapy for advanced ovarian cancer prolongs time to relapse and progression-free survival (PFS) by an average of 5.6 months, compared with placebo, report authors of a double-blind phase 3 clinical trial presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Pazopanib maintenance therapy significantly extends time without recurrence and thus increases PFS and delays the need for further chemotherapy in ovarian cancer patients,” said Andreas du Bois, MD, of the Kliniken Essen Mitte in Essen, Germany. “This is the first phase 3 maintenance study demonstrating superior outcome for a targeted therapy.  Therefore, pazopanib might be a valuable option for women with FIGO stage II-IV ovarian, fallopian tube, or peritoneal cancer who have not progressed after receiving first-line chemotherapy.”

Pazopanib is an oral multi-targeted tyrosine kinase inhibitor that has already been approved by the FDA for kidney cancer and soft tissue sarcoma therapy.  It targets ATP binding sites at VEGF, PDGF, and c-KIT receptors.

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A total of 940 patients were randomly assigned to receive placebo or pazopanib (800 mg once daily) for up to 24 months. At a median follow-up of 24 months, patients assigned to receive pazopanib had longer PFS than those administered placebo (median, 17.9  vs. 12.3 months; hazard ratio [HR], 0.766; 95% CI: 0.64-0.91; P=0.0021). The result was robust and persisted in subgroup analyses of age, Eastern Cooperative Oncology Group status, and histology.

Mean exposure for pazopanib was shorter than for placebo (9.9 vs. 11.7 months), Dr. du Bois noted.

“Pazopanib treatment was associated with a higher incidence of adverse events (AEs) and serious AEs (26% vs. 11%) vs. placebo,” Dr. du Bois reported. “The most common AEs were hypertension, diarrhea, nausea, headache, fatigue, and neutropenia.”

Grade 3/4 adverse events included hypertension (6% in placebo-group patients vs. 31% in pazopanib group patients), liver-related toxicity (<1% placebo vs. 9% pazopanib), neutropenia (2% placebo vs. 10% pazopanib), and diarrhea (1% vs. 8%), Dr. du Bois reported. Three patients in the pazopanib group and one patient on placebo died of serious AEs.

Overall survival data are “completely immature” but currently show no trend, Dr. du Bois concluded.

The study was supported by GlaxoSmithKline.