Pazopanib Added to Paclitaxel Does Not Improve Ovarian Cancer Outcomes

The addition of pazopanib to paclitaxel failed to improve outcomes over paclitaxel alone in a phase II study of women with persistent or recurrent pretreated epithelial ovarian cancer. The results of the study were published in JAMA Oncology.

“Multiple reports have shown that angiogenesis is associated with worse survival for patients with ovarian cancer,” wrote study authors led by Debra L. Richardson, MD, of the University of Texas Southwestern Medical Center in Dallas. Bevacizumab, which targets VEGF, is approved in certain ovarian cancer patients, so researchers hypothesized that pazopanib, which has multiple targets including VEGF receptors 1, 2, and 3; PDGF receptors alpha and beta; and c-KIT, might also improve outcomes for these patients.

The phase II trial was a randomized double-blind study that included 106 women with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. All patients had received 1 to 3 prior regimens, and had a performance status of 0 to 2; they were randomized to receive paclitaxel plus pazopanib (54 patients) or paclitaxel plus placebo (52 patients).

The median follow-up period was 17.7 months, during which time 84 progression-free survival events occurred; 44.4% of pazopanib and 38.5% of placebo patients had died. The median progression-free survival was 7.5 months with the study drug and 6.2 months with placebo, for a hazard ratio (HR) of 0.84 (90% CI, 0.57–1.22; P = .20).

The overall survival was also similar, with a median of 20.7 months with pazopanib and 23.3 months with placebo, for an HR of 1.04 (90% CI, 0.60–1.79; P = .90). The response rate was 31.8% with pazopanib and 22.7% with placebo.

More placebo patients stopped therapy due to disease progression compared with pazopanib patients (65.4% vs 31.5%), while more in the pazopanib group stopped due to adverse events (37% vs 9.6%; P = .001). The most common adverse events that led to treatment discontinuation were neutropenia and neuropathy. Neutropenia was the most common grade 3/4 adverse event, but the authors noted that febrile neutropenia was uncommon in the study.

“This study indicates that the combination of weekly paclitaxel with pazopanib is not superior to weekly paclitaxel alone in women with recurrent ovarian, fallopian tube, and primary peritoneal cancer,” the authors concluded. “Results from this study do not support further investigation of this combination in this patient population at these doses and schedule.”