AUA 2022: Changes in Pituitary–Gonadal Hormones After Enzalutamide or Abiraterone Plus Prednisone in Men With Castration-Resistant Prostate Cancer (HEAT): Results From a Randomised Clinical Trial

(UroToday.com) In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Ternov discussed changes in pituitary-gonadal hormones after enzalutamide or abiraterone plus prednisone in men with metastatic castration-resistant prostate cancer (mCRPC) based on results from the randomized HEAT trial.

Both abiraterone acetate with prednisone and enzalutamide are guideline-recommended treatment options for mCRPC that target the androgen receptor pathway. While abiraterone acetate inhibits androgen production, enzalutamide blocks androgen receptor signaling. Thus, given these different mechanisms of action, the authors sought to assess differential effects on the hormones of the pituitary-gonadal axis.

To do so, they used the HEAT phase IV randomized controlled trial. This trial enrolled men with progressive metastatic prostate cancer and castrate levels of testosterone (<1.7 nmol/L). Patients were randomized in a 1:1 fashion to first-line enzalutamide (160 mg/day) or abiraterone acetate (1000 mg) with 10 mg prednisone/day. The authors assessed fasting serum hormones, including testosterone, free-testosterone, sexual hormone-binding globulin (SHGB), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), using the gold standard assay liquid chromatography – tandem mass spectrometry before 11 am at baseline and at 12-week post-intervention. The change in hormone levels between baseline and 12-weeks after the start of therapy was compared between treatment arms with logarithmic mixed models analysis, and the within-subject change for each treatment group was analyzed with a logarithmic paired samples t-test.

Between June 2017 and September 2019, the authors randomized 170 participants to receive enzalutamide (n=84 analysed) or abiraterone acetate (n=85 analysed). Compared to patients receiving abiraterone, those treated with enzalutamide had a 19.9% higher increase in FSH. Conversely, a larger decline in testosterone and SHGB was found for those patients receiving abiraterone acetate. Additionally, a greater proportion of patients receiving abiraterone acetate (83 of 85) had lower than detectable levels of free-testosterone than the enzalutamide group (6 or 84) (chi-square test p <0.001). 

Thus, the authors conclude that while clinical experience has demonstrated that both of these agents are effective in mCRPC, their differing mechanism of action results in different pituitary-gonadal hormonal profiles.


Presented by: Klara Kvorning Ternov, MD – Herlev and Gentofte Hospital