Comparing ARPIs and Docetaxel in mHSPC: Insights From the STOPCAP IPD Meta-Analysis

A meta-analysis of individual participant data (IPD) from the STOPCAP trial presented at the American Society of Clinical Oncology 2025 Genitourinary Cancers Symposium sought to determine which patients with metastatic hormone-sensitive prostate cancer (mHSPC) may benefit more from treatment using androgen receptor pathway inhibitors (ARPIs) over docetaxel with an androgen deprivation therapy (ADT) doublet.

Data from completed trials investigating ARPI effects in mHSPC were analyzed. The impact of ARPIs was first assessed using an intention-to-treat, two-stage, common-effect meta-analysis of hazard ratios (HRs), adjusting for key covariates and concomitant docetaxel use.

The primary effects were based on overall survival (OS), and interaction effects were initially evaluated using progression-free survival (PFS) to enhance statistical power, then OS, if PFS interactions were significant (P<.10). In clinically relevant subgroups, ARPI and docetaxel doublet effects were compared through a two-stage, contrast-based, random-effects network meta-analysis (NMA).

By October 2024, updated IPD from five trial comparisons were collected, including LATITUDE, STAMPEDE A vs G, SWOG-1216, ENZAMET, and STAMPEDE A vs J. Based on 2,882 events that occurred among 5,472 patients, the addition of an ARPI to ADT improved OS rates (HR, 0.69; 95% CI, 0.64-0.74).

An analysis of four trial comparisons (excluding SWOG-1216) with PFS data (2,781 events among 4,161 patients) showed improved PFS (HR, 0.49; 95% CI, 0.45-0.53) through the use of ARPIs, with a benefit that increased with younger age (interaction P=.034), higher BMI (interaction P=.048), and lower burden of metastases (interaction P=.096).

Similar trends were observed for OS (age interaction, P=.035; BMI interaction, P=.031; volume interaction, P=.25), and the age effect was most pronounced in the abiraterone trials. An NMA combining IPD from the ARPI plus ADT and docetaxel plus ADT trials (GETUG-AFU-15, CHAARTED, STAMPEDE A vs C) suggested that ARPI doublets may improve OS more than a docetaxel doublet (HR, 0.85; 95% CI, 0.70-1.03).

However, in patients with high-volume, synchronous disease, where docetaxel is more effective, (excluding SWOG-1216, as data were not available), effects on OS were as follows: HR, 0.89 and 95% CI, 0.74-1.06.

The study’s findings suggest that patients with mHSPC who are younger, have a higher BMI, or have low-volume disease may benefit more from treatment with ARPIs; ARPI and docetaxel doublets seem to be similarly effective in treatment of high-volume, synchronous disease. Ongoing IPD collection will further clarify the role of ARPI doublets versus triplet therapy, including docetaxel, in optimizing personalized treatment.