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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2017

Open Access 01-11-2017 | Clinical trial

IPET study: an FLT-PET window study to assess the activity of the steroid sulfatase inhibitor irosustat in early breast cancer

Authors: Carlo Palmieri, Richard Szydlo, Marie Miller, Laura Barker, Neva H. Patel, Hironobu Sasano, Tara Barwick, Henry Tam, Dimitri Hadjiminas, Jasmin Lee, Abeer Shaaban, Hanna Nicholas, R. Charles Coombes, Laura M. Kenny

Published in: Breast Cancer Research and Treatment | Issue 2/2017

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Abstract

Background

Steroid sulfatase (STS) is involved in oestrogen biosynthesis and irosustat is a first generation, irreversible steroid sulfatase inhibitor. A pre-surgical window-of-opportunity study with irosustat was undertaken in estrogen receptor-positive (ER+) breast cancer to assess the effect of irosustat on tumour cell proliferation as measured by 3′-deoxy-3′-[18F] fluorothymidine uptake measured by PET scanning (FLT-PET) and Ki67.

Methods

Postmenopausal women with untreated ER+ early breast cancer were recruited, and imaged with FLT-PET at baseline and after at least 2 weeks treatment with irosustat, 40 mg once daily orally. The primary endpoint was changed in FLT uptake; secondary endpoints included safety and tolerability of irosustat, changes in tumoral Ki67 and steroidogenic enzymes expression and circulating steroid hormone levels.

Results

Thirteen women were recruited, and ten started irosustat for 2 weeks, followed by repeat FLT-PET scans in eight. Defining response as decreases of ≥20% in standardized uptake value (SUV) or ≥30% in Ki, 1 (12.5% (95% CI 2–47%, p = 0.001)) and 3 (43% (95% CI 16–75%, p = <0.001) patients, respectively, responded. 6 out of 7 patients had a Ki67 reduction (range = −19.3 to 76.4%), and median percentage difference in Ki67 was 52.3% (p = 0.028). In one patient with a low baseline STS expression, a 19.7% increase in Ki67 was recorded. STS decreases were seen in tumours with high basal STS expression, significant decreases were also noted in aromatase, and 17β-hydroxysteroid dehydrogenase type 1 and 2. Irosustat was generally well tolerated with all adverse event CTCAE Grade ≤2.

Conclusions

Irosustat resulted in a significant reduction in FLT uptake and Ki67, and is well tolerated. These data are the first demonstrating clinical activity of irosustat in early breast cancer. Baseline expression of STS may be a biomarker of sensitivity to irosustat.
Appendix
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Metadata
Title
IPET study: an FLT-PET window study to assess the activity of the steroid sulfatase inhibitor irosustat in early breast cancer
Authors
Carlo Palmieri
Richard Szydlo
Marie Miller
Laura Barker
Neva H. Patel
Hironobu Sasano
Tara Barwick
Henry Tam
Dimitri Hadjiminas
Jasmin Lee
Abeer Shaaban
Hanna Nicholas
R. Charles Coombes
Laura M. Kenny
Publication date
01-11-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4427-x

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