[<sup>18</sup>F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 31754793.
- Also identified by DOI 10.1007/s00259-019-04532-z and PMC identifier 7101300.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sub>v</sub>β<sub>3</sub> and α<sub>v</sub>β<sub>5</sub> are both upregulated in tumor-associated vasculature. [<sup>18</sup>F]Fluciclatide is a novel PET tracer that has high affinity for integrins α<sub>v</sub>β<sub>3/5</sub>, and was used to assess the anti-angiogenic effect of pazopanib. 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<sup>2</sup>). Following completion of 18 weeks of combination therapy, patients continued with single-agent pazopanib until disease progression. Dynamic [<sup>18</sup>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. 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 [<sup>18</sup>F]fluciclatide uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and fibroblast growth factor (FGF) were predictive of greater reduction in SUV<sub>60,mean</sub> following pazopanib. Kinetic modeling of PET data indicated a reduction in K<sub>1</sub> and K<sub>i</sub> following pazopanib indicating reduced radioligand delivery and retention. Combination therapy followed by maintenance pazopanib is effective and tolerable in platinum-resistant/refractory ovarian cancer. [<sup>18</sup>F]Fluciclatide-PET uptake parameters predict clinical outcome with pazopanib therapy indicating an anti-angiogenic response.
Medical subject headings
- Ovarian Neoplasms
- Paclitaxel