Apalutamide Reduces Risk of Death by 51% in Metastatic CSPC

Treatment with apalutamide (Erleada) exhibited a 51% reduction in the risk of death compared with darolutamide (Nubeqa) without docetaxel for the treatment of patients with metastatic castration-sensitive prostate cancer (CSPC) after 24 months of follow-up (HR, 0.49; 95% CI, 0.30-0.83; P = .007) in a presentation given at the 36th Annual International Prostate Cancer Update (IPCU), according to a news release from the developer, Johnson & Johnson.¹

According to the developers, the study included a protocol pre-specified primary end point of overall survival (OS), which was designed to meet FDA guidance. Patients were identified between August 2022 and June 2025. Additionally, the OS data build upon findings from the phase 3 multinational, double-blind TITAN trial (NCT02489318).

After a median follow up of 22.7 months in the phase 3 trial, which evaluated apalutamide plus androgen deprivation therapy (ADT) vs placebo plus ADT in patients with metastatic CSPC, a 33% reduction in the risk of death was observed with apalutamide (HR, 0.67; 95% CI, 0.51-0.89; P = .005).² A final analysis of the TITAN trial reported a 35% reduction in the risk of death after a median follow up of 44 months (HR, 0.65; 95% CI, 0.53-0.79; P < .0001). Additionally, a 24-month OS rate of 92.1% in the real-world analysis was consistent with the 82.4% rate in the TITAN trial.

Additional findings from the trial revealed a 48-month OS rate of 65.1% among patients who initiated treatment with apalutamide at the final analysis of the TITAN trial.

“These real-world data show the survival benefit of apalutamide vs darolutamide in patients with [metastatic] CSPC without the concurrent use of docetaxel. The results are consistent with other datasets showing similar [OS] benefit vs other commonly used agents,” Mehmet Bilen, MD, director of the Genitourinary Medical Oncology Program at Winship Cancer Institute of Emory University, said in the news release.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 the phase 3 TITAN trial, 1052 patients with metastatic CSPC were randomly assigned to receive apalutamide (n = 525) or placebo (n = 527), with patients in the placebo arm given the option to cross over to apalutamide following unblinding of the trial.

In the experimental and placebo arms, the median age was 69 years (range, 45-94) vs 68 years (range, 43-90), and most patients in each arm had a Gleason score of more than 7 (66.9% vs 67.9%). Additionally, most patients had an ECOG performance score of 0 (62.5% vs 66.0%), high disease volume (61.9% vs 63.6%). A total of 11.0% vs 10.4% of patients received previous docetaxel, and 17.9% vs 15.0% received prior therapy for localized disease.

The dual primary end points were OS and radiographic progression-free survival (PFS). Secondary end points included time to initiation of cytotoxic chemotherapy, time to pain progression, time to chronic opioid use, and time to skeletal-related events.

Overall incidence of treatment-emergent adverse effects (TEAEs) was similar between the apalutamide, placebo, and crossover groups, with exposure-adjusted rates of TEAEs of interest per 100 patient-years of 40.0%, 22.4%, and 41.9%, respectively. Furthermore, cumulative rates of first grade 3 or 4 TEAEs and serious AEs were also similar between each group.

“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, concluded in the release.¹ “We have now seen in repeated real-world examinations the [OS] benefit of apalutamide versus other agents and this head-to-head analysis supports apalutamide being a key standard of care treatment for patients with [metastatic] CSPC.”

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, 2025. https://tinyurl.com/45b73b9b
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