Apalutamide is linked to fewer CNS-related conditions in patients with nmCRPC

A retrospective analysis evaluating new-onset central nervous system (CNS) conditions in patients receiving an androgen receptor pathway inhibitor (ARPI) for nonmetastatic castration resistant prostate cancer (nmCRPC) indicated a lower incidence of these issues with apalutamide (Erleada) compared with darolutamide (Nubeqa) and enzalutamide (Xtandi), according to research presented at the 2025 Society of Urology Oncology Annual Meeting in Phoenix, Arizona.¹

Previous research has pointed to the importance of weighing CNS conditions including cognitive impairment, falls, seizures, fatigue, pain, and headaches in patients with mCRPC who are treated with an ARPI.^2-3

In their poster, the authors, led by Charmi Patel, MD, explained that “real-world evidence on CNS-related clinical outcomes in patients with nmCRPC remains limited.”

The investigators performed a retrospective analysis using linked clinical data derived from community urology practices in the US as well as administrative claims data. Patients were allocated to mutually exclusive cohorts based on first dispensation or paid pharmacy claim for apalutamide, darolutamide, or enzalutamide. The outcome of the study was newly diagnosed CNS conditions not seen during the 12-month baseline period among patients who initiated an ARPI.

Regarding baseline characteristics, 253 patients initiated treatment with apalutamide, 544 initiated treatment with darolutamide, and 645 patients initiated treatment with enzalutamide. Mean age was 77.7 years, 81.0 years, and 79.0 years respectively. Across the cohorts, 246 (97.2%) patients, 529 (97.2%) patients, and 620 (96.1%) had previously been treated with androgen deprivation therapy, respectively.

Mean duration of on-treatment observation period was 12 months (median, 7.4 months) for patients receiving apalutamide, 14.0 months (median, 9.3 months) in patients receiving darolutamide, and 12.3 months (median, 7.7 months) in patients receiving enzalutamide.

The investigators reported that new onset of CNS-related conditions was lower in patients in the apalutamide cohort at 12 months (apalutamide, 25.7%, darolutamide, 31.4%, enzalutamide, 40.8%) and 24 months (apalutamide: 46.6%, darolutamide: 54.6%, enzalutamide: 59.7%) post index. The median time-to-new onset of CNS-related conditions was 29.2 months in the apalutamide cohort vs 21.3 months in the darolutamide cohort and 18.1 months in the enzalutamide cohort. In addition, rates of commonly observed new-onset conditions such as fatigue, falls, dizziness, pain, and weakness were also numerically lower in patients receiving apalutamide vs patients receiving enzalutamide or darolutamide.

“These findings suggest a clinical difference in the real-world incidence of CNS-related conditions among patients treated with different ARPIs, suggesting that apalutamide may have a more favorable profile that minimizes the risk of CNS-related conditions in patients with nmCRPC. Ongoing research and long-term monitoring are needed to further characterize CNS-related outcomes and guide optimal treatment selection in this patient population,” the authors wrote in their poster.

REFERENCES

1. Real-world assessment of new-onset central nervous system conditions in patients with non-metastatic castration-resistant prostate cancer treated with apalutamide, darolutamide, or enzalutamide. Presented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Abstract 3. https://suo-abstracts.secure-platform.com/a/gallery/rounds/24/details/4576

2. Bubendorf L, Schöpfer A, Wagner U, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000 May;31(5):578-83. doi:10.1053/hp.2000.6698

3. Markman M. Early recognition of spinal cord compression in cancer patients. Cleve Clin J Med. 1999;66(10):629-31. doi:10.3949/ccjm.66.10.629