Pazopanib Plus Paclitaxel Does Not Improve Outcomes in Recurrent Ovarian Cancer
Angiogenesis in ovarian cancer is associated with worse survival
Pazopanib plus weekly paclitaxel does not improve survival outcomes compared with paclitaxel alone among women with recurrent ovarian cancer, according to study findings published in JAMA Oncology.
Studies have demonstrated that angiogenesis in ovarian cancer is associated with worse survival. Pazopanib is a tyrosine kinase inhibitor that targets the vascular endothelial growth factor (VEGF) 1, 2, and 3, and has been effective as maintenance therapy.
For this double-blind phase 2 study, researchers randomly assigned 106 women with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma to receive intravenous paclitaxel 80 mg/m2 plus oral pazopanib 800 mg or placebo. Eligible patients must have undergone at least 1 platinum-based chemotherapy regimen and up to 2 cytotoxic regimens with no more than 1 nontaxane, nonplatinum regimen.
The median follow-up time was 17.7 months, and the response rate was 31.8% and 22.7% in the pazopanib arm compared with the placebo arm, respectively.
Median progression-free survival was 7.5 months in the pazopanib arm vs 6.2 months in the placebo arm (hazard ratio [HR], 0.84; 90% CI, 0.57-1.22; P =.20).
Median overall survival (OS) was 20.7 months in the pazopanib arm vs 23.3 months in the placebo arm (HR, 1.04; 90% CI, 0.60-1.79; P =.90).
More patients in the pazopanib arm discontinued treatment because of adverse events; notably, severe hypertension occurred more commonly in the pazopanib arm.
The rate of treatment discontinuation because of disease-progression was higher in the paclitaxel arm compared with the pazopanib arm.
Single-nucleotide polymorphisms (eg, interleukin 8 and hypoxia-inducible factor 1α) was not found to be associated with overall survival and patient response, and patients with the VEGFA CC genotype may be more resistant to paclitaxel compared with patients with the AC or AA genotype.
The researchers concluded that “the addition of pazopanib to weekly paclitaxel in women with recurrent ovarian cancer increased toxic effects and did not significantly improve patient outcomes. Results from this study do not support further investigation of this combination in this patient population at these doses and schedule.”
Richardson DL, Sill MW, Coleman RL, et al. Paclitaxel with and without pazopanib for persistent or recurrent ovarian cancer [published online December 14, 2017]. JAMA Oncol. doi: 10.1001/jamaoncol.2017.4218