Retrospective, Real-World Analysis Shows Improved OS With Apalutamide Over Darolutamide in mCSPC

Patients with metastatic castration-sensitive prostate cancer (mCSPC) who initiated apalutamide (Erleada) plus androgen deprivation therapy (ADT) without docetaxel in routine clinical practice in the United States experienced a statistically significant overall survival (OS) advantage vs those who initiated darolutamide (Nubeqa) plus ADT without docetaxel, according to findings from a retrospective, real-world, head-to-head analysis. ¹

The study included patients who started apalutamide (n = 1460) or darolutamide (n = 287) between August 2022 and June 2025 and applied propensity score matching to adjust for baseline differences in measured characteristics, supporting a more balanced comparison of outcomes between treatment cohorts. With 24 months of follow-up, initiation of apalutamide without docetaxel was associated with a 51% reduction in the risk of death compared with darolutamide without docetaxel (HR, 0.49; 95% CI, 0.30-0.83; P = .007).

The data were presented at the 36th Annual International Prostate Cancer Update in February.

“These real-world data show the survival benefit of apalutamide vs darolutamide in patients with mCSPC without the concurrent use of docetaxel. The results are consistent with other data sets showing similar OS benefit vs other commonly used agents,” Mehmet A. Bilen, MD, director of the Genitourinary Medical Oncology Program at Winship Cancer Institute of Emory University, shared in a news release. “This real-world analysis utilized large contemporary data sets using rigorous methodology to support clinical decision-making in the absence of prospective head-to-head studies that are likely impractical to conduct.”

The findings build on results from the phase 3 TITAN trial (NCT02489318).^1,2 Data from the primary analysis showed a statistically significant OS benefit with apalutamide plus ADT vs ADT alone after a median follow-up of 22.7 months (HR, 0.67; 95% CI, 0.51-0.89; P = .005). This benefit was maintained at the final analysis after a median follow-up of 44 months (HR, 0.65; 95% CI, 0.53-0.79; P < .0001). According to Johnson & Johnson, the proportion of patients alive at 24 months in the apalutamide cohort of the current real-world analysis (92.1%) was generally consistent with the 24-month OS rate reported in TITAN (82.4%).¹

How Was This Real-World Analysis Designed?

This retrospective, real-world analysis was structured to meet FDA expectations for real-world evidence; it leveraged large, contemporary data sets representative of routine clinical practice, used peer-reviewed analytic methods, and incorporated strict study monitoring.

In the study, both apalutamide and darolutamide were assessed in the absence of docetaxel. To enable a balanced head-to-head comparison, the analysis used propensity score–based methods to account for baseline differences in measured patient characteristics.

“Real-world comparisons can provide critical information to support patient care when conducted in a rigorous and methodologically sound manner,” Mahadi Baig, MD, MHCM, vice president of US medical affairs at Johnson & Johnson Innovative Medicine, noted in the news release. “We have now seen in repeated real-world examinations the overall survival benefit of apalutamide vs other agents and this head-to-head analysis supports apalutamide being a key standard of care treatment for patients with mCSPC.”

What Should Be Known About Apalutamide’s Safety Profile?

In the TITAN trial, ischemic cardiovascular adverse effects (AEs) occurred in 4.4% of patients treated with apalutamide vs 1.5% with placebo. Across the phase 3 SPARTAN (NCT01946204) and TITAN trials, deaths due to ischemic cardiovascular AEs occurred in 0.3% of patients receiving apalutamide and 0.2% receiving placebo. Patients with unstable angina, myocardial infarction, congestive heart failure, stroke, or transient ischemic attack within 6 months of randomization were excluded from both trials.

Investigators also observed cerebrovascular AEs. In SPARTAN, cerebrovascular effects occurred in 2.5% of patients receiving apalutamide vs 1.0% with placebo. In TITAN, cerebrovascular AEs occurred in 1.9% of patients receiving apalutamide vs 2.1% with placebo. Across SPARTAN and TITAN, deaths due to cerebrovascular AEs occurred in 0.2% of patients in both the apalutamide and placebo arms.

Apart from cardiovascular and cerebrovascular safety, the most common adverse effects in at least 10% of patients treated with apalutamide (≥ 2% absolute difference over placebo) across TITAN and SPARTAN were fatigue, arthralgia, rash, decreased appetite, fall, weight decrease, hypertension, hot flush, diarrhea, and fracture.

References

1. Real-world head-to-head analysis shows 51% reduction in risk of death for patients with metastatic castration-sensitive prostate cancer treated with Erleada (apalutamide) versus darolutamide without docetaxel through 24 months. News release. Johnson & Johnson. February 2, 2026. Accessed February 2, 2026. https://www.jnj.com/media-center/press-releases/real-world-head-to-head-analysis-shows-51-reduction-in-risk-of-death-for-patients-with-metastatic-castration-sensitive-prostate-cancer-treated-with-erleada-apalutamide-versus-darolutamide-without-docetaxel-through-24-months
2. Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-2303. doi:10.1200/JCO.20.03488