A Phase 1b and Randomized Phase 2 Trial of Pazopanib with or Without Fosbretabulin in Advanced Recurrent Ovarian Cancer
Targeting angiogenesis is a well-established treatment strategy in a variety of tumor types, although for ovarian cancer, improvements in progression-free survival (PFS) have been modest. To improve their efficacy, combinations of antivascular agents may be considered. In this phase 1b/randomized phase 2 study, Morgan and colleagues evaluated pazopanib, an oral VEGFR inhibitor, with or without fosbretabulin, an intravenous vascular disrupting agent, in patients with advanced recurrent ovarian cancer.
Patients in the randomized phase 2 study (n = 21) received either 54 mg/m2 fosbretabulin and 600 mg/day pazopanib or 800 mg/day pazopanib alone. Median PFS was numerically greater for the fosbretabulin/pazopanib combination (7.6 months [95% confidence interval (CI), 4.1-not estimated]) than for the pazopanib alone group (3.7 months [95% CI, 1.0-8.1]; hazard ratio, 0.30; 95% CI, 0.08-1.03; P = .06). However, observed cardiac toxicity resulted in premature discontinuation of the trial, as 4 patients who received fosbretabulin/pazopanib (2 [16.7%] in phase 1b [n = 12], and 2 [9.5%] in the randomized phase 2 study) developed acute hypertension plus reversible secondary cardiac toxicity.
Although the fosbretabulin/pazopanib combination showed preliminary efficacy in treating recurrent epithelial ovarian cancer, reversible secondary cardiac toxicity associated with the treatment resulted in the premature discontinuation of the trial. The study investigators suggest that improved hypertension control may have prevented this toxicity.
Morgan RD, et al. ESMO 2018. Abstract 956P.