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

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Title: [18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer
Authors: Sharma, R
Valls, PO
Inglese, M
Dubash, S
Chen, M
Gabra, H
Montes, A
Challapalli, A
Arshad, M
Tharakan, G
Chambers, E
Cole, T
Lozano-Kuehne, JP
Barwick, TD
Aboagye, EO
Item Type: Journal Article
Abstract: 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-angiogenic response.
Issue Date: 21-Nov-2019
Date of Acceptance: 11-Sep-2019
URI: http://hdl.handle.net/10044/1/75363
DOI: 10.1007/s00259-019-04532-z
ISSN: 0340-6997
Publisher: Springer Verlag
Journal / Book Title: European Journal of Nuclear Medicine and Molecular Imaging
Copyright Statement: © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust
Funder's Grant Number: RDC04 79560
MR/N020782/1
RDC04
RDB22 79560
Keywords: Angiogenesis
Ovarian cancer
PET imaging
Pazopanib
Platinum resistance
[18F]Fluciclatide
Angiogenesis
Ovarian cancer
PET imaging
Pazopanib
Platinum resistance
[18F]Fluciclatide
1103 Clinical Sciences
0299 Other Physical Sciences
Nuclear Medicine & Medical Imaging
Publication Status: Published online
Conference Place: Germany
Online Publication Date: 2019-11-21
Appears in Collections:Division of Surgery
Division of Cancer



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