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

Jorianne Boers; Clasina M Venema; Erik F J de Vries; Geke A P Hospers; Hendrikus H Boersma; Bart Rikhof; Christine Dorbritz; Andor W J M Glaudemans; Carolina P Schröder

doi:10.1016/j.ejca.2020.11.008

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

Eur J Cancer. 2021 Feb:144:151-161. doi: 10.1016/j.ejca.2020.11.008. Epub 2020 Dec 18.

Authors

Jorianne Boers¹, Clasina M Venema¹, Erik F J de Vries², Geke A P Hospers¹, Hendrikus H Boersma³, Bart Rikhof⁴, Christine Dorbritz⁵, Andor W J M Glaudemans², Carolina P Schröder⁶

Affiliations

¹ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
² Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
³ Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁴ Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
⁵ Medical Imaging Center, Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁶ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: c.p.schroder@umcg.nl.

PMID: 33341447
DOI: 10.1016/j.ejca.2020.11.008

Abstract

Background: The androgen receptor (AR) is a potential target in metastatic breast cancer (MBC), and 16β-[¹⁸F]-fluoro-5α-dihydrotestosterone positron emission tomography ([¹⁸F]-FDHT-PET) can be used for noninvasive visualisation of AR. [¹⁸F]-FDHT uptake reduction during AR-targeting therapy reflects AR occupancy and might be predictive for treatment response. We assessed the feasibility of [¹⁸F]-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 [¹⁸F]-FDHT-PET at baseline and after 4-6 weeks bicalutamide treatment. Baseline [¹⁸F]-FDHT uptake was expressed as maximum standardised uptake value. Percentage change in tracer uptake, corrected for background activity (SUV_cor), 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 [¹⁸F]-FDHT-PET in 21 patients detected 341 of 515 lesions found with standard imaging and 21 new lesions. Follow-up [¹⁸F]-FDHT-PET was evaluable in 17 patients with 349 lesions, showing a decrease in median SUV_cor 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 [¹⁸F]-FDHT uptake could be detected by follow-up [¹⁸F]-FDHT-PET in patients with AR + MBC. However, this change could not predict bicalutamide response.

Clinical trial information: NCT02697032.

Keywords: Androgen receptor; Bicalutamide; Metastatic breast cancer; [(18)F]-FDHT-PET.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Androgen Antagonists / therapeutic use*
Anilides / therapeutic use*
Breast Neoplasms / diagnostic imaging
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism
Breast Neoplasms / pathology*
Dihydrotestosterone / metabolism*
Female
Fluorine Radioisotopes / metabolism*
Follow-Up Studies
Humans
Neoplasm Metastasis
Nitriles / therapeutic use*
Positron-Emission Tomography / methods*
Prognosis
Prospective Studies
Radiopharmaceuticals / metabolism
Receptors, Androgen / chemistry*
Tosyl Compounds / therapeutic use*

Substances

AR protein, human
Androgen Antagonists
Anilides
Fluorine Radioisotopes
Nitriles
Radiopharmaceuticals
Receptors, Androgen
Tosyl Compounds
Dihydrotestosterone
bicalutamide

Associated data

ClinicalTrials.gov/NCT02697032