Real-World Head-to-Head Analysis Reveals 51% Lower Risk of Death in Metastatic Castration-Sensitive Prostate Cancer Patients Treated with ERLEADA® (Apalutamide) Compared to Darolutamide—Without Docetaxel—Over 24 Months
Johnson & Johnson today announced new real world head-to-head evidence demonstrating that patients with metastatic castration-sensitive prostate cancer (mCSPC) initiating ERLEADA® without docetaxel experienced a statistically significant 51 percent reduction in the risk of death compared to those who initiated on darolutamide without docetaxel through 24-months of follow-up (hazard ratio [HR] 0.49; 95% confidence interval [CI], 0.30–0.83; P=0.007). These findings reflecting patients treated in routine clinical practice are being presented at the 36th Annual International Prostate Cancer Update on February 2, where it was selected as a top abstract (Abstract #6).
Designed to meet rigorous FDA guidance and robust methodological framework on real-world evidence, this study included a pre-specified protocol, pre-specified primary endpoint of overall survival (OS), power calculation, and propensity score matching through inverse probability of treatment weighting (IPTW).1,2,3 Together, these methodological safeguards deliver robust, reproducible insights that inform real-world treatment decisions. The retrospective study identified mCSPC patients who initiated ERLEADA® or darolutamide without docetaxel between August 2022 and June 2025. There were 1,460 ERLEADA® patients and 287 darolutamide initiators who met study criteria.
“These real-world data show the survival benefit of apalutamide versus darolutamide in patients with mCSPC without the concurrent use of docetaxel. The results are consistent with other datasets showing similar overall survival benefit versus other commonly used agents,” said Mehmet Bilen, M.D. Director, Genitourinary Medical Oncology Program, Winship Cancer Institute of Emory University.* “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.”
As reported previously, ERLEADA® plus androgen deprivation therapy (ADT) treatment shows rapid and deep prostate-specific antigen (PSA) decline that was associated with prolonged OS.4,5 These real-world OS data build upon findings from the Phase 3 multinational, double-blinded, placebo-controlled TITAN trial, which evaluated mCSPC patients (n=1052) randomized (1:1) receiving either ERLEADA® 240 mg once daily (n=525) or placebo once daily (n=527).4
“Real-world comparisons can provide critical information to support patient care when conducted in a rigorous and methodologically sound manner,” said Mahadi Baig, M.D., M.H.C.M., Vice President, U.S. Medical Affairs, Johnson & Johnson Innovative Medicine. “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.”
TITAN demonstrated a statistically significant OS benefit for mCSPC patients treated with ERLEADA® plus ADT compared to ADT alone at the primary analysis after a median 22.7 months of follow-up (HR 0.67; 95% CI, 0.51-0.89; P=0.005) and at the final analysis after a median 44 months of follow-up (HR 0.65; 95% CI, 0.53-0.79; P<0.0001).4,5 The proportion of patients alive at 24 months (92.1 percent) observed in the ERLEADA® cohort in this real-world analysis is generally consistent with that reported in TITAN (82.4 percent). All patients in the TITAN trial received a concomitant gonadotropin-releasing hormone agonist (GnRH) analog or had a prior bilateral orchiectomy. The dual primary endpoints were OS and radiographic progression-free survival (rPFS).
About the Study
These real-world findings adhere to the rigorous standards set by the U.S. FDA, including providing comparative effectiveness evidence from large, contemporary U.S. datasets used in routine clinical practice, peer-reviewed methods, and strict study monitoring. Complementing randomized controlled trials, real-world evidence can help inform clinical decisions, including comparative data into treatments, by collecting a plethora of data from a diverse range of patients in the real-world setting.
In this real-world analysis, both ERLEADA® and darolutamide were administered without docetaxel. Study investigators applied propensity score matching (PSM) to match the apalutamide and darolutamide groups through adjusting for baseline differences in measured patient characteristics. PSM is employed in observational studies to support fair comparison of outcomes.
Some limitations of this study include potential miscoding or missing information in the data sources; however, the data sources used in this study were deemed fit for purpose to identify the patient population correctly and to assess survival. IPTW, a propensity score matching statistical method, was employed to balance baseline characteristics between treatment groups, removing bias from measured confounders and replicating the conditions of a randomized clinical trial.
About Prostate Cancer
Approximately 330,000 people are diagnosed with prostate cancer each year in the U.S.6 Up to 40 percent of patients will be classified as high-risk.7 Despite advancements in treatment, disease recurrence remains substantial; up to 50 percent of patients within ten years of surgery experience recurrence and carry a significant risk of disease progression and death.7 It’s estimated that more than 36,000 men will succumb to prostate cancer in 2026, which reinforces the importance of choosing the best possible therapy early for patients with advanced prostate cancer.6
About ERLEADA®
ERLEADA® (apalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). ERLEADA® received U.S. Food and Administration (FDA) approval for nmCRPC in February 2018 and received U.S. FDA approval for mCSPC in September 2019.ERLEADA® is the first and only next-generation androgen receptor inhibitor offering a once-daily, single-tablet treatment option for patients. To date, more than 325,000 patients worldwide have been treated with ERLEADA®. Additional studies are ongoing in the evaluation of ERLEADA® for the treatment of localized high-risk or locally advanced prostate cancer including, the Phase 3 ATLAS (NCT02531516) and PROTEUS (NCT03767244) studies.
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