Johnson & Johnson announced results from a real-world, head-to-head study demonstrating that apalutamide (ERLEADA®) provided a statistically significant overall survival benefit compared to enzalutamide in patients with metastatic castration-sensitive prostate cancer (mCSPC). The study, involving nearly 4,000 patients, was presented at the 6th European Congress of Oncology Pharmacy (ECOP) in Lisbon, Portugal.
The retrospective study, which applied U.S. Food and Drug Administration (FDA) real-world evidence guidance, identified mCSPC patients who initiated apalutamide or enzalutamide between December 16, 2018, and December 31, 2023, using electronic databases. The analysis included 1,800 apalutamide initiators and 1,909 enzalutamide initiators meeting the study criteria.
Key Findings
The analysis revealed that patients with mCSPC who initiated apalutamide as their first androgen receptor pathway inhibitor (ARPI) experienced a statistically significant 23% reduction in the risk of death at 24 months compared to those who initiated enzalutamide (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.62-0.96; P < 0.019). The proportion of patients alive at 24 months in the apalutamide cohort was 87.6%, consistent with the Phase 3 TITAN trial (82.4%).
Supporting Evidence from TITAN Trial
The Phase 3 TITAN trial previously demonstrated a statistically significant superior overall survival benefit of apalutamide plus androgen deprivation therapy (ADT) compared to ADT alone. Primary analysis after a median of 22.7 months of follow-up showed an HR of 0.67 (95% CI, 0.51-0.89; P = 0.005), and final analysis after a median of 44 months of follow-up showed an HR of 0.65 (95% CI, 0.53-0.79; P < 0.0001).
Expert Commentary
"This real-world evidence showed a statistically significant and clinically meaningful improvement in survival with apalutamide over enzalutamide in patients with mCSPC at 24 months," said Neal Shore, M.D., F.A.C.S., Steering Committee Chair and Medical Director, Carolina Urologic Research Center and study investigator. He emphasized the value of real-world data in the absence of prospective ARPI comparator trials.
Luca Dezzani, M.D., U.S. Vice President, Medical Affairs, Solid Tumors, Johnson & Johnson Innovative Medicine, highlighted that apalutamide is the only ARPI to demonstrate a survival benefit as early as 22 months, as seen in the TITAN study. He noted that this study provides additional evidence supporting the overall survival benefit of apalutamide.
Limitations
The study's limitations include potential miscoding or missing information in the data sources. However, the data sources were deemed fit for identifying the patient population and assessing survival. While survival was assessed at 24 months, longer-term studies are needed to fully evaluate the therapeutic effects of these treatments.
Prostate Cancer Context
Approximately 300,000 people are diagnosed with prostate cancer each year in the U.S., with up to 40% classified as high-risk. Despite treatment advancements, recurrence remains substantial, with up to 50% of patients experiencing recurrence within ten years of surgery. It is estimated that more than 35,000 men will die from prostate cancer in 2024, underscoring the importance of optimal early therapy.
About Apalutamide
Apalutamide (ERLEADA®) is an androgen receptor inhibitor indicated for treating patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and mCSPC. It received FDA approval for nmCRPC in February 2018 and for mCSPC in September 2019. Apalutamide is a once-daily, single-tablet treatment, with over 200,000 patients treated worldwide. Ongoing studies are evaluating apalutamide for localized high-risk or locally advanced prostate cancer.
