[ 18 F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer

Background Angiogenesis is 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 α v β 3 and α v β 5 are both upregulated in tumor-associated vasculature. [ 18 F]Fluciclatide is a novel PET tracer that has high affinity for integrins α v β 3/5 , and was used to assess the anti-angiogenic effect of pazopanib. Patients and 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 (800 mg daily) followed by combination therapy with weekly paclitaxel (80 mg/m 2 ). Following completion of 18 weeks of combination therapy, patients continued with single-agent pazopanib until disease progression. Dynamic [ 18 F]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 responses were seen in seven patients (54%). Median progression-free survival (PFS) was 10.63 months, and overall survival (OS) was 18.5 months. Baseline [ 18 F]fluciclatide uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and fibroblast growth factor (FGF) were predictive of greater reduction in SUV 60,mean following pazopanib. Kinetic modeling of PET data indicated a reduction in K 1 and K i following pazopanib indicating reduced radioligand delivery and retention. Conclusions Combination therapy followed by maintenance pazopanib is effective and tolerable in platinum-resistant/refractory ovarian cancer. [ 18 F]Fluciclatide-PET uptake parameters predict clinical outcome with pazopanib therapy indicating an anti-angiogenic response.