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

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Abstract

Background: The androgen receptor (AR) is a potential target in metastatic breast cancer (MBC), and 16 beta-[F-18]-fluoro-5 alpha-dihydrotestosterone positron emission tomography ([F-18]-FDHT-PET) can be used for noninvasive visualisation of AR. [F-18]-FDHT uptake reduction during AR-targeting therapy reflects AR occupancy and might be predictive for treatment response. We assessed the feasibility of [F-18]-FDHT-PET to detect changes in AR availability during bicalutamide treatment and correlated these changes with treatment response.

Patients and methods: Patients with AR thorn MBC, regardless of oestrogen receptor status, received an [F-18]-FDHT-PET at baseline and after 4-6 weeks bicalutamide treatment. Baseline [F-18]-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 [F-18]-FDHT-PET in 21 patients detected 341 of 515 lesions found with standard imaging and 21 new lesions. Follow-up [F-18]-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 Z 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 Z 0.338).

Conclusion: In this feasibility study, a bicalutamide-induced reduction in [F-18]-FDHT uptake could be detected by follow-up [F-18]-FDHT-PET in patients with AR thorn MBC. However, this change could not predict bicalutamide response. (C) 2020 The Authors. Published by Elsevier Ltd.

Original languageEnglish
Pages (from-to)151-161
Number of pages11
JournalEuropean Journal of Cancer
Volume144
Early online date17-Dec-2020
DOIs
Publication statusPublished - Feb-2021

Keywords

  • Bicalutamide
  • Metastatic breast cancer
  • Androgen receptor
  • [F-18]-FDHT-PET
  • PROSTATE-CANCER
  • ABIRATERONE ACETATE
  • EXPRESSION
  • ESTROGEN
  • MONOTHERAPY
  • PHARMACOKINETICS
  • ENZALUTAMIDE
  • TOLERABILITY
  • ANTIANDROGEN
  • COMBINATION

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