Do androgen receptor inhibitors offer a survival edge over abiraterone?

Clinical takeaway: For patients with metastatic hormone-sensitive prostate cancer (mHSPC) receiving androgen deprivation therapy (ADT) intensification, treatment with the androgen receptor inhibitors (ARIs) apalutamide or enzalutamide was associated with longer overall survival than abiraterone in routine clinical practice. These findings may help inform treatment selection and patient counseling, although randomized head-to-head trials are still needed.

Both ARIs and abiraterone have improved outcomes when added to ADT for mHSPC, but no randomized trial has directly compared the two approaches. Real-world studies have reached conflicting conclusions, leaving clinicians with little clear guidance when choosing among effective options.

In this retrospective analysis of the Flatiron Health database, researchers evaluated 3,404 patients with mHSPC treated in US community and academic oncology practices. Of these, 1,830 received abiraterone and 1,574 received an ARI (507 apalutamide, 1,067 enzalutamide). Median follow-up was about 26 months.

After adjustment for baseline differences, patients treated with an ARI had a 26% lower risk of death than those treated with abiraterone. Limiting the analysis to patients diagnosed after mid-December 2019 yielded a 33% lower risk.

The survival gap widened over time. At 12 months, overall survival was 92.6% with an ARI versus 89.6% with abiraterone; by 24 months, it was 84.7% versus 77.8%.

Median overall survival was estimated at 67.9 months with an ARI versus 57.2 months with abiraterone, although the authors noted that follow-up remained shorter than these median survival times.

The study was retrospective and subject to residual confounding. Selection bias is also possible because patients with fewer financial barriers may have been more likely to receive ARIs than lower-cost abiraterone. Darolutamide was not evaluated.

The authors wrote: “However, given conflicting clinical practice data across differing database populations, only a randomized clinical trial can definitively answer this question.”

Source: Gebrael G, et al. (2026 Oct 20) JAMA Network Open. Androgen synthesis inhibitors vs androgen receptor inhibitors and survival in metastatic hormone-sensitive prostate cancer