SUMMARY  

• Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia.¹ Please refer to local labeling for additional considerations and data.
• In SPARTAN, the phase 3 study in patients with non-metastatic castration-resistant prostate cancer (nmCRPC; N=1207), at the final analysis of overall survival (OS), which occurred after a median follow-up of 52 months, adverse events (AEs) of hypertension were reported in 28%, 21%, and 11% of patients in the ERLEADA, placebo, and crossover groups, respectively.²
• In TITAN, the phase 3 study in patients with metastatic castration-sensitive prostate cancer (mCSPC; N=1052), at the final analysis of OS, which occurred after a median follow-up of 44.0 months, AEs of hypertension occurred in 19.5%, 15.9%, and 6.3% of patients in the ERLEADA, placebo, and crossover groups, respectively.^3,4

CLINICAL DATA

Phase 3 Study in Patients With nmCRPC (SPARTAN)

The SPARTAN study evaluated the efficacy and safety of ERLEADA in patients with nmCRPC who had a prostate-specific antigen doubling time (PSADT) of ≤10 months and confirmation of non-metastatic disease by blinded independent central review (N=1207).⁵

Study Design/Methods

• Patients were randomized 2:1 to receive either ERLEADA 240 mg orally once daily (n=806) or placebo once daily (n=401).⁵
• All patients in the study received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a prior bilateral orchiectomy.⁶
• Study exclusion criteria related to hypertension:
  • History of uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg). Patients with a history of uncontrolled hypertension could participate in the study if blood pressure was controlled by anti-hypertensive treatment.⁶
• Patient baseline demographic and disease characteristics were well balanced, and there were no significant differences between groups. The median age of patients in both treatment groups was 74 years.⁵ 75% (599 out of 803) and 76% (302 out of 398) of patients in the ERLEADA and placebo safety populations, respectively, had a history of cardiac disorders, diabetes, or hypertension.⁷
• The median treatment duration at primary analysis was 16.9 months in the ERLEADA group and 11.2 months in the placebo group.⁷ After unblinding of the study, 76 (19%) patients in the placebo group received therapy with ERLEADA plus ADT (crossover group). At the final analysis for OS, after a median follow-up of 52 months, the median treatment duration was 32.9 months in the ERLEADA group, 11.5 months in the placebo group, and 26.1 months in the crossover group.²

Safety

• AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.⁵
• Rates of hypertension are reported in Table: Hypertension in the SPARTAN Study shown below.
  • When adjusted for exposure, the incidence of hypertension was similar between treatment arms (36.3 events per 100 patient-years in the ERLEADA arm vs 38.7 events per 100 patient-years in the placebo arm).⁵

Additional Information

Additional information regarding the SPARTAN study, including the clinical study report, protocol, and statistical analysis plan, can be found at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/Erleada_210951_toc.cfm (scroll to the “Sponsor Clinical Study Reports ARN-509-003 SPARTAN NCT # 01946204” section at the bottom of the web page).

Phase 3 Study in Patients With mCSPC (TITAN)

The TITAN study evaluated the efficacy and safety of ERLEADA in patients with mCSPC (N=1052).⁹

Study Design/Methods

• Patients were randomized 1:1 to receive either ERLEADA 240 mg orally once daily (n=525) or placebo once daily (n=527).⁹
• All patients in the study received a concomitant GnRH analog or had a prior bilateral orchiectomy.¹⁰
• Study exclusion criteria related to hypertension:
  • Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg). Patients with a history of hypertension could participate in the study if blood pressure was controlled by anti-hypertensive treatment.¹⁰
• Patient baseline demographic and disease characteristics were well balanced, and there were no substantial differences between groups. The median age of patients in the ERLEADA group and placebo group was 69 years and 68 years, respectively.⁹ 66.2% (347 out of 524) and 60.7% (320 out of 527) of patients in the ERLEADA and placebo safety populations, respectively, had a history of cardiac disorders, diabetes, or hypertension.¹¹
• The median treatment duration was 20.5 months in the ERLEADA group and 18.3 months in the placebo group.⁹ After unblinding of the study, 208 (39.5%) patients in the placebo group received therapy with ERLEADA plus ADT (crossover group). At the final analysis for OS, after a median follow-up of 44.0 months, the median treatment duration was 39.3 months in the ERLEADA group, 20.2 months in the placebo group, and 15.4 months in the crossover group.³

Safety

• AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.3.⁹
• Rates of hypertension are reported in Table: Hypertension in the TITAN Study shown below.

• Figure: Cumulative Incidence of First Treatment-Emergent Hypertension Event details the cumulative incidence of any-grade hypertension between the ERLEADA (n=524) and placebo (n=527) groups with respect to time in months.⁴

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 20 November 2024. Summarized in this response are relevant data limited to the phase 3 SPARTAN and TITAN studies in patients with nmCRPC and mCSPC, respectively.