Abstract

3070 Background: Angiogenesis has been shown to be a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum resistant/refractory ovarian cancer. Integrins αvβ3 and αvβ5 are both up-regulated in tumour-associated vasculature. [18F]Fluciclatide is a novel PET tracer that has high affinity for integrins αvβ3/5, and was used to assess the anti-angiogenic effect of pazopanib. Methods: We conducted an open-label, phase Ib study in patients with platinum resistant/refractory ovarian cancer. Patients received 1 week of single agent pazopanib (800mg daily) followed by combination therapy with weekly paclitaxel 80mg/m2. Following completion of 18 weeks of therapy, patients continued with single agent pazopanib until disease progression. Dynamic [18F]Fluciclatide-PET imaging was conducted at baseline and after 1 week of pazopanib. Response (RECIST 1.1), toxicities and survival outcomes were recorded. Circulating markers of angiogenesis were assessed with therapy. Results: Fourteen patients were included in the intention-to-treat analysis. Complete and partial response was seen in 7 patients (54%). Median progression free survival (PFS) was 7.97 months, and overall survival (OS) was 18.5 months. A reduction in [18F]fluciclatide uptake was observed following 1 week of pazopanib, and the reduction in uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and FGF were predictive of greater reduction in SUV60,mean following pazopanib. Kinetic modelling indicated a reduction in K1 and Ki following pazopanib indicating reduced radiotracer delivery and retention. Conclusions: Combination therapy followed by maintenance pazopanib is effective and tolerable in patients with platinum resistant/refractory ovarian cancer. We have shown that [18F]fluciclatide-PET uptake parameters alter with pazopanib therapy indicating an anti-angiogenic response. Clinical trial information: NCT01608009.

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