Real-World PSA Response and Overall Survival Among Men with mCSPC Receiving Apalutamide Versus Darolutamide (Both Without Docetaxel) in the US

To date, no head-to-head comparisons of apalutamide versus darolutamide have been reported for metastatic castration-sensitive prostate cancer (mCSPC). This study compared prostate-specific antigen decline ≥ 90% (PSA90) and overall survival (OS) between apalutamide and darolutamide, both without docetaxel, among patients with mCSPC in real-world clinical practice in the USA. Men diagnosed with mCSPC who initiated apalutamide or darolutamide between 2022 and 2025 were identified from linked electronic medical records and insurance claims. The apalutamide and darolutamide cohorts were balanced using inverse probability of treatment weighting. PSA90 response was assessed on-treatment. The proportions of patients achieving a PSA90 response and OS through a maximum of 6 months and 24 months post-treatment initiation, respectively, were compared between the two cohorts using weighted Kaplan-Meier and weighted Cox proportional hazards models. For PSA90 analyses, weighted characteristics were well balanced between the apalutamide (n = 714; mean age 73.9 years, 59.6% White, 21.2% Black, 13.7% other, 5.5% unknown race) and darolutamide cohorts (n = 145; mean age 74.3 years, 58.8% White, 21.6% Black, 15.0% other, 4.7% unknown race). PSA90 response rates through 6 months were 49% higher for apalutamide than for darolutamide (weighted hazard ratio [HR]: 1.49 [95% confidence interval (CI) 1.07, 2.07]; p = 0.017). For OS analyses, weighted characteristics were also well balanced between apalutamide (n = 1460; mean age 73.5 years, 59.6% White, 21.5% Black, 13.5% other, 5.4% unknown race) and darolutamide (n = 287; mean age 73.7 years, 60.0% White, 22.4% Black, 12.4% other, 5.2% unknown race). Apalutamide was associated with a 51% lower rate of mortality relative to darolutamide through 24 months (weighted HR: 0.49 [95% CI 0.30, 0.83]; p = 0.007). Among patients with mCSPC treated without docetaxel, apalutamide was associated with higher PSA90 response rates and lower mortality than darolutamide. These findings indicate a potential difference in disease control and survival between the two androgen receptor-targeted agents in routine clinical practice. Apalutamide and darolutamide are medications that block hormone activity that fuels prostate cancer growth. They are currently approved to treat metastatic castration-sensitive prostate cancer (mCSPC) with standard hormone-lowering combination therapy (androgen-deprivation therapy, ADT). This study used medical and insurance data from US community urology practices to compare outcomes between patients with mCSPC who started apalutamide (1460 patients) or darolutamide (287 patients), both without docetaxel. Apalutamide was FDA approved for this use throughout the study period. Darolutamide without docetaxel was FDA approved only near the end of the study period (June 2025) but was still widely used in US urology practices during this time. Statistical methods were used to standardize patient features between the two groups by weighting them for specific measured differences in patient and disease characteristics. Overall, 74.6% of patients treated with apalutamide and 56.1% of patients receiving darolutamide achieved ≥ 90% drop in prostate-specific antigen (PSA, a prostate cancer marker) levels among those tested within 6 months of starting treatment, a 49% increase in the rate of PSA response for apalutamide. Additionally, 24 months after starting treatment, 92.1% of patients who received apalutamide and 85.8% of patients who received darolutamide remained alive, a 51% lower rate of death with apalutamide. While these findings are subject to limitations, discussed in the full manuscript, they suggest that in clinical practice and without chemotherapy intensification, apalutamide may provide better disease control and longer overall survival than darolutamide in patients with mCSPC. Notably, no prior studies have directly compared these two treatments for these outcomes.