Serial [18F]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer. (February 2021)

• Record Type: Journal Article
• Authors: Boers, Jorianne; Venema, Clasina M.; de Vries, Erik F.J.; Hospers, Geke A.P.; Boersma, Hendrikus H.; Rikhof, Bart; Dorbritz, Christine; Glaudemans, Andor W.J.M.; Schröder, Carolina P.
• Is Part Of: European journal of cancer. Volume 144(2021)
• Page Start: 151
• Page End: 161
• Publication Date: 2021-02
• Subjects: Bicalutamide -- Metastatic breast cancer -- Androgen receptor -- [18F]-FDHT-PET; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2020.11.008
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: The androgen receptor (AR) is a potential target in metastatic breast cancer (MBC), and 16β-[ 18 F]-fluoro-5α-dihydrotestosterone positron emission tomography ([ 18 F]-FDHT-PET) can be used for noninvasive visualisation of AR. [ 18 F]-FDHT uptake reduction during AR-targeting therapy reflects AR occupancy and might be predictive for treatment response. We assessed the feasibility of [ 18 F]-FDHT-PET to detect changes in AR availability during bicalutamide treatment and correlated these changes with treatment response. Patients and methods: Patients with AR + MBC, regardless of oestrogen receptor status, received an [ 18 F]-FDHT-PET at baseline and after 4–6 weeks bicalutamide treatment. Baseline [ 18 F]-FDHT uptake was expressed as maximum standardised uptake value. Percentage change in tracer uptake, corrected for background activity (SUVcor ), between baseline and follow-up PET scan (% reduction), was assessed per-patient and lesion. Clinical benefit was determined in accordance with Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or clinical evaluation (absence of disease progression for ≥24 weeks). Results: Baseline [ 18 F]-FDHT-PET in 21 patients detected 341 of 515 lesions found with standard imaging and 21 new lesions. Follow-up [ 18 F]-FDHT-PET was evaluable in 17 patients with 349 lesions, showing a decrease in median SUVcor from 1.3 to 0.7 per-patient and lesion ( P < 0.001). Median % reduction per-patient was −45% and per-lesion −39%. In patients with progressive disease ( n = 11), median % reduction was −30% versus −53% for patients who showed clinical benefit (in accordance with RECIST ( n = 3) or clinical evaluation ( n = 3); P = 0.338). Conclusion: In this feasibility study, a bicalutamide-induced reduction in [ 18 F]-FDHT uptake could be detected by follow-up [ 18 F]-FDHT-PET in patients with AR + MBC. However, this change could not predict bicalutamide response. Clinical trial information: NCT02697032. Highlights: The androgen receptor (AR) is a potential therapy target in breast cancer. Blocking AR can possibly be guided by AR visualisation with 16β-[ 18 F]-fluoro-5α-dihydrotestosterone positron emission tomography ([ 18 F]-FDHT-PET). Bicalutamide-induced changes in AR availability could be detected by [ 18 F]-FDHT-PET. The largest effect of AR blockade on [ 18 F]-FDHT-PET was seen in oestrogen receptor negative – metastases.