Comprehensive Evaluation of Androgen Receptor Pathway Inhibitors in Metastatic Castration-Sensitive Prostate Cancer:...

Area of Science:

• Oncology
• Prostate Cancer Research
• Clinical Pharmacology

Background:

• Androgen receptor pathway inhibitors (ARPIs) combined with androgen deprivation therapy (ADT) are standard for metastatic castration-sensitive prostate cancer (mCSPC).
• Limited comparative data exist for individual ARPIs and their use after castration resistance develops.

Purpose of the Study:

• To compare the efficacy and outcomes of first-line ARPIs (abiraterone, enzalutamide, apalutamide) in mCSPC.
• To evaluate the impact of PSA response patterns on time to castration resistance and overall survival.

Main Methods:

• Multicenter retrospective study of 274 mCSPC patients treated with first-line ARPI (2018-2023).
• Inverse probability of treatment weighting (IPTW) balanced baseline characteristics.
• Patients categorized by PSA response: early, delayed, early relapse, and nonresponse.

Main Results:

• After IPTW, no significant differences in time to castration-resistant prostate cancer (CRPC) or overall survival (OS) were observed among abiraterone, enzalutamide, and apalutamide.
• Apalutamide was associated with more grade ≥2 toxicities and dose modifications.
• Sustained PSA suppression <0.2 ng/mL for 12 months correlated with favorable outcomes, irrespective of response speed.

Conclusions:

• Abiraterone, enzalutamide, and apalutamide demonstrate equivalent efficacy in mCSPC when baseline imbalances are controlled.
• Sustained PSA suppression is a strong predictor of favorable prognosis.
• First-line docetaxel and ARPI showed comparable OS in patients who developed CRPC.