| Title |
[18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer
|
|---|---|
| Published in |
European Journal of Nuclear Medicine and Molecular Imaging, November 2019
|
| DOI | 10.1007/s00259-019-04532-z |
| Pubmed ID | |
| Authors |
Rohini Sharma, Pablo Oriol Valls, Marianna Inglese, Suraiya Dubash, Michelle Chen, Hani Gabra, Ana Montes, Amarnath Challapalli, Mubarik Arshad, George Tharakan, Ed Chambers, Tom Cole, Jingky P. Lozano-Kuehne, Tara D. Barwick, Eric O. Aboagye |
| 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 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. 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. 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. 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. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 19 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 26% |
| Student > Doctoral Student | 4 | 21% |
| Student > Master | 3 | 16% |
| Student > Bachelor | 1 | 5% |
| Unspecified | 1 | 5% |
| Other | 2 | 11% |
| Unknown | 3 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 42% |
| Biochemistry, Genetics and Molecular Biology | 3 | 16% |
| Neuroscience | 2 | 11% |
| Agricultural and Biological Sciences | 1 | 5% |
| Physics and Astronomy | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 3 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 November 2019.
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#21,153,429
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Outputs from European Journal of Nuclear Medicine and Molecular Imaging
#2,610
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#388,224
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Outputs of similar age from European Journal of Nuclear Medicine and Molecular Imaging
#61
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