Serum Androgens as Predictive Biomarkers: Results From a Randomized Clinical Trial Comparing Enzalutamide and Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer

• Published in: Clinical genitourinary cancer 2024-12, Vol.22 (6), p.102200, Article 102200
• Main Authors: Ternov, Klara K., Fode, Mikkel, Sønksen, Jens, Bisbjerg, Rasmus, Lindberg, Henriette, Palapattu, Ganesh, Bratt, Ola, Østergren, Peter B.
• Format: Article
• Language: English
• Subjects: Abiraterone acetate; Abiraterone Acetate - administration & dosage; Abiraterone Acetate - therapeutic use; Aged; Aged, 80 and over; Androgens; Androgens - blood; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides; Biomarkers, Tumor - blood; Cancer and Oncology; Cancer och onkologi; Enzalutamide; Humans; Male; Middle Aged; Nitriles - therapeutic use; Phenylthiohydantoin - administration & dosage; Phenylthiohydantoin - analogs & derivatives; Phenylthiohydantoin - therapeutic use; Prednisone - administration & dosage; Prednisone - therapeutic use; Progression-Free Survival; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant - blood; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - mortality; Prostatic Neoplasms, Castration-Resistant - pathology; Testosterone; Testosterone - blood; Treatment Outcome
• ISSN: 1558-7673; 1938-0682; 1938-0682
• DOI: 10.1016/j.clgc.2024.102200

The purpose of this study was to investigate the association between baseline androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line enzalutamide or abiraterone acetate plus prednisone (AAP). We previously randomized men with mCRPC to enzalutamide or AAP to compare side-effects and measured androgen concentrations. In this post-hoc analysis, patients were grouped in quartiles (Q) based on their serum androgen values. Kaplan-Meier and Cox regression were used to analyze progression-free and overall survival for baseline androgen groups, treatment subgroups and their interaction. The trial was registered at clinicaltrialsregister.eu (2017-000099-27). Eighty-four patients received enzalutamide and 85 AAP. Overall, higher (Q4) compared with lower (Q1) baseline serum testosterone was associated with longer progression-free survival (24.8 vs. 10.7 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.33; 0.84) and overall survival (52.8 vs. 31.5 months, HR 0.49, 95% CI 0.28; 0.85). The risk reduction in death seemed to be treatment dependent (treatment subgroup interaction P = .04). For men in the AAP subgroup, the Q4 compared with Q1 group had a significant lower risk of death (HR 0.30, 95% CI 0.13; 0.73), while no difference was found for enzalutamide (HR 0.77, 95% CI 0.35; 1.69). Similar results were found for the other androgens. Pre-treatment serum testosterone levels may be a clinically useful biomarker for predicting mCRPC treatment responses and guiding treatment selection. We compared baseline serum androgen concentrations and outcomes in men with metastatic castration-resistant prostate cancer treated with enzalutamide or abiraterone in a post-hoc analysis based on data from a randomized clinical trial of 169 patients. Higher compared with lower testosterone was associated with longer progression-free and overall survival. Testosterone levels may be a clinically useful for guiding treatment selection.