ARIs Linked to Longer Survival Than Abiraterone in Metastatic Hormone-Sensitive Prostate Cancer

Treatment intensification with a next-generation androgen receptor inhibitor (ARI) was associated with longer overall survival than intensification with the androgen synthesis inhibitor abiraterone acetate in patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to a retrospective cohort study published in JAMA Network Open.

The investigators noted that randomized trials have established both drug classes when added to androgen deprivation therapy (ADT) compared with ADT alone, but no randomized trials have compared the classes directly, and studies from clinical practice have produced conflicting results.

Using the nationwide US Flatiron Health electronic health record–derived database of community and academic practices, the researchers identified 3,404 patients diagnosed with mHSPC from 2013 to 2024 who initiated abiraterone (1,830 patients) or an ARI, apalutamide (507) or enzalutamide (1,067), within 3 months before or 6 months after diagnosis. Patients previously treated with docetaxel were excluded. After inverse probability of treatment weighting, median overall survival was 67.9 months with an ARI and 57.2 months with abiraterone (hazard ratio, 0.74; 95% CI, 0.64-0.87). At 24 months, overall survival was 84.7% and 77.8%, respectively, an absolute difference of 6.9 percentage points.

Results were similar when therapy initiation was used as the index date and when the analysis was restricted to patients indexed on or after December 16, 2019. The association did not differ significantly by insurance status or area-level socioeconomic status.

The authors noted that the median follow-up of 25.6 months was shorter than the estimated median survival in both groups and that fewer than a quarter of patients had died, so median survival estimates should be interpreted with caution. Other limitations included the retrospective design, missing data, potential residual confounding, and possible selection bias, because more stable patients with fewer financial barriers may have been preferentially prescribed ARIs over lower-cost abiraterone. The authors said randomized clinical trials are needed for a definitive answer.

Source: Gebrael G, Jo Y, Nandakumar V, et al. Androgen synthesis inhibitors vs androgen receptor inhibitors and survival in metastatic hormone-sensitive prostate cancer. JAMA Netw Open. 2026;9(10):e2639458. doi:10.1001/jamanetworkopen.2026.39458