Introduction/Background Patients with recurrent ovarian cancer (ROC) have a particularly poor prognosis. So far recurrent treatment are mostly restricted by previous toxicity and of limited activity. The role of adding modern multi-targeted tyrosine kinase inhibitors (TKIs) for targeting angiogenesis could be a proimising therapeutic strategy. The investigator-initiated multicentre TOPAZ trial aimed to evaluate the safety and efficacy of the combination of Topotecan with Pazopanib.
Methodology Patients with platinum-resistant ROC with no more than two prior lines of chemotherapy were enrolled. The chemotherapy backbone was based on weekly Topotecan (4 mg/m2, d1,8,15 q28d). In phase I, pazopanib was added orally 400 mg/d in a dose-escalating regime to determine the maximum tolerated dose (MTD). The aim of phase II was to evaluate the safety and efficacy of pazopanib in the optimal MTD together with weekly Topotecan based on progression-free survival.
Results From June 2012 to February 2017, 11 patients were enrolled in phase I and 50 patients in phase II. The MTD of pazopanib was set at 400 mg/d. In phase I, the most common adverse event was haematological toxicity. In phase II, the median progression-free survival was 3,5 months (95% CI:2.0–5.0 months), with haematological toxicity being the most common reason for dose change and treatment delays. The combination of Topotecan and Pazopanib is shown to be feasibble in terms of safety profile. It offers no clinical advantage in progression-free or overall survival compared to Topotecan monotherapy.
Conclusion Adding pazopanib to topotecan is safe and feasible, but does not seem to have any clinical benefit. We will not pursue this combination. Further studies are needed that pursue the approach of novel combination therapies with chemotherapy and anti-angiogenesis inhibitors. In addition, the promising therapeutic options with PARP and immune checkpoint inhibitors should also be considered.
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