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@article{Sharma:2020:10.1007/s00259-019-04532-z,
author = {Sharma, R and Valls, PO and Inglese, M and Dubash, S and Chen, M and Gabra, H and Montes, A and Challapalli, A and Arshad, M and Tharakan, G and Chambers, E and Cole, T and Lozano-Kuehne, JP and Barwick, TD and Aboagye, EO},
doi = {10.1007/s00259-019-04532-z},
journal = {European Journal of Nuclear Medicine and Molecular Imaging},
pages = {1239--1251},
title = {[18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer},
url = {http://dx.doi.org/10.1007/s00259-019-04532-z},
volume = {47},
year = {2020}
}

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TY  - JOUR
AB  - 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 αvβ3 and αvβ5 are both upregulated in tumor-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. 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/m2). Following completion of 18 weeks of combination 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 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 [18F]fluciclatide uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and fibroblast growth factor (FGF) were predictive of greater reduction in SUV60,mean following pazopanib. Kinetic modeling of PET data indicated a reduction in K1 and Ki 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. [18F]Fluciclatide-PET uptake parameters predict clinical outcome with pazopanib therapy indicating an anti
AU  - Sharma,R
AU  - Valls,PO
AU  - Inglese,M
AU  - Dubash,S
AU  - Chen,M
AU  - Gabra,H
AU  - Montes,A
AU  - Challapalli,A
AU  - Arshad,M
AU  - Tharakan,G
AU  - Chambers,E
AU  - Cole,T
AU  - Lozano-Kuehne,JP
AU  - Barwick,TD
AU  - Aboagye,EO
DO  - 10.1007/s00259-019-04532-z
EP  - 1251
PY  - 2020///
SN  - 0340-6997
SP  - 1239
TI  - [18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer
T2  - European Journal of Nuclear Medicine and Molecular Imaging
UR  - http://dx.doi.org/10.1007/s00259-019-04532-z
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31754793
UR  - https://link.springer.com/article/10.1007%2Fs00259-019-04532-z
UR  - http://hdl.handle.net/10044/1/75363
VL  - 47
ER  -

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