Abstract
Purpose
To evaluate the real-world comparative effectiveness of androgen receptor pathway inhibitors (ARPIs)—abiraterone, apalutamide, enzalutamide—and docetaxel, plus androgen-deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC).
Methods
We identified US men with mHSPC who initiated ADT within 4 months of diagnosis and were treated with abiraterone, apalutamide, enzalutamide, or docetaxel within 4 months of ADT initiation between January 2019 and December 2023, with follow-up through June 2025. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included time to metastatic castration-resistant prostate cancer (mCRPC) progression (TTP) and time to new treatment initiation (TTNT). Cox proportional hazard and Fine-Gray models with overlapping propensity score weights were used to estimate primary and secondary outcomes, respectively. Subgroup analyses by timing of metastasis and sensitivity analyses using inverse probability of treatment weights were conducted for primary outcomes.
Results
Among 9,141 US men with mHSPC, ARPI doublets demonstrated superior PFS versus docetaxel doublets (abiraterone: adjusted hazard ratio [aHR], 0.60 [95% CI, 0.55 to 0.66]; apalutamide: aHR, 0.64 [95% CI, 0.56 to 0.73]; enzalutamide: aHR, 0.57 [95% CI, 0.51 to 0.64]), with no significant differences among ARPI regimens. OS was comparable among all doublet regimens. Neither PFS nor OS differed by timing of disease. TTP (abiraterone: aHR, 0.52 [95% CI, 0.47 to 0.58]; apalutamide: aHR, 0.59 [95% CI, 0.52 to 0.68]; enzalutamide: aHR, 0.51 [95% CI, 0.45 to 0.57]) and TTNT (abiraterone: aHR, 0.46 [95% CI, 0.42 to 0.51]; apalutamide: aHR, 0.53 [95% CI, 0.46 to 0.61]; enzalutamide: aHR, 0.47 [95% CI, 0.42 to 0.53]) showed similar patterns favoring ARPI doublets. Sensitivity analyses showed consistent findings.
Conclusion
ARPI doublets demonstrated superior PFS but similar OS compared with docetaxel doublet, with no differences among individual ARPIs. Patients receiving ARPI doublets were less likely to progress to mCRPC or initiate new treatment.