Head-to-head analysis shows OS benefit with apalutamide vs darolutamide in mCSPC

Findings from a real-world head-to-head analysis demonstrated that treatment with apalutamide (Erleada) conferred a statistically significant improvement in overall survival (OS) compared with darolutamide (Nubeqa) without concurrent docetaxel in patients with metastatic castration-sensitive prostate cancer (mCSPC) who had not received prior treatment with an androgen receptor pathway inhibitor (ARPI).^1,2

The results were presented at the 36th International Prostate Cancer Update in Vail, Colorado.

“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 datasets showing similar overall survival benefit vs other commonly used agents,” said Mehmet A. Bilen, MD, Director of the Genitourinary Medical Oncology Program at the Winship Cancer Institute of Emory University in Atlanta, Georgia, in a news release on the findings.¹ “This real-world analysis utilized large contemporary datasets using rigorous methodology to support clinical decision-making in the absence of prospective head-to-head studies that are likely impractical to conduct.”

In total, the retrospective intention-to-treat analysis included 1747 patients, of whom 1460 received apalutamide without docetaxel and 287 received darolutamide without docetaxel. The median time between metastasis and initiation of an ARPI was 4.1 months in the apalutamide cohort and 2.9 months in the darolutamide cohort.

At the 24-month time point, patients who received apalutamide demonstrated a 51% reduction in the risk of death compared with patients who received darolutamide (HR, 0.49; 95% CI, 0.30 to 0.83; P = .007). These results were consistent when assessing OS using all follow-up (HR, 0.51; 95% CI, 0.32 to 0.82).

According to the authors, the findings indicate that apalutamide confers an OS benefit vs darolutamide without the need for treatment intensification with docetaxel. The results build on previous data from the phase 3 TITAN trial (NCT02489318), which demonstrated that patients with mCSPC who received treatment with apalutamide plus androgen deprivation therapy (ADT) had a statistically significant improvement in OS vs those who received ADT alone.³

TITAN included a total of 1052 patients with mCSPC who were randomly assigned 1:1 to receive 240 mg apalutamide once daily plus ADT (n = 525) or placebo plus ADT once daily (n = 527). In the final OS analysis at a median follow-up of 44 months, apalutamide plus ADT significantly reduced the risk of death by 35% vs ADT alone (HR, 0.65; 95% CI, 0.53 to 0.79; P < .0001). After accounting for crossover, apalutamide plus ADT showed a 48% reduction in the risk of death (HR, 0.52; 95% CI, 0.42 to 0.64; P < .0001).

The proportion of patients alive at 24 months in the TITAN trial was 82.4%. The recent real-world analysis of apalutaide vs darolutamide was consistent with these results, showing a proportion of 92.1% in the apalutamide cohort.

“Real-world comparisons can provide critical information to support patient care when conducted in a rigorous and methodologically sound manner,” said Mahadi Baig, MD, MHCM, Vice President of US Medical Affairs at Johnson & Johnson Innovative Medicine, in the news release.² “We have now seen in repeated real-world examinations the overall survival benefit of apalutamide versus other agents and this head-to-head analysis supports apalutamide being a key standard of care treatment for patients with mCSPC.”

REFERENCES

1. Lowentritt B, Bilen MA, Singhal M, et al. Real-World Comparison of Overall Survival In Patients with Metastatic Castration-Sensitive Prostate Cancer Initiating Apalutamide Without Docetaxel Versus Darolutamide Without Docetaxel. Presented at: 36th International Prostate Cancer Update. February 1-4, 2026. Vail, Colorado. https://grandroundsinurology.com/wp-content/uploads/2026/02/final.Poster_Abstracts_IPCU2026.pdf

2. 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 3, 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

3. 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