SUMMARY

• In SPARTAN, the phase 3 study evaluating the safety and efficacy of ERLEADA plus androgen deprivation therapy (ADT) versus placebo plus ADT in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), breast disorder treatment-emergent adverse events (TEAEs) occurred infrequently in both the ERLEADA and placebo groups.^1,2
  • Gynecomastia was reported in 28 (3.5%) and 8 (2.0%) patients in the ERLEADA and placebo groups, respectively, with no grade 3-4 AEs reported. When adjusted for exposure, the incidence of gynecomastia was 2.4 events per 100 patient-years in the ERLEADA group and 2.2 events per 100 patient-years in the placebo group.²
  • All other breast disorder TEAEs (breast tenderness, breast mass, breast pain, and nipple pain) were reported in <1% of patients in both groups with 1 report of a grade 3 breast mass in the ERLEADA group.²
• In TITAN, the phase 3 study evaluating the safety and efficacy of ERLEADA plus ADT versus placebo plus ADT in patients with metastatic castration-sensitive prostate cancer (mCSPC), breast disorder TEAEs occurred infrequently in both the ERLEADA and placebo groups.^3-5
  • Gynecomastia was reported in 10 (1.9%), 6 (1.1%), and 0 patients in the ERLEADA, placebo, and crossover groups, respectively. Grade 3 gynecomastia was reported in 1 patient treated with ERLEADA.⁵
  • All other breast disorder TEAEs (breast pain, nipple pain, breast tenderness, breast enlargement, and bilateral breast buds) were reported in <1% of patients in all groups, with no reports of grade 3-4 AEs.⁵

CLINICAL DATA

Phase 3 SPARTAN Study in Patients with nmCRPC

The SPARTAN study evaluated the efficacy and safety of ERLEADA in patients with nmCRPC (N=1207).¹ Patients were required to have a prostate-specific antigen doubling time of ≤10 months and confirmation of non-metastatic disease by blinded independent central review. Patients were randomized 2:1 to receive either ERLEADA 240 mg orally (PO) once daily (QD; n=806) or placebo QD (n=401). All patients in the SPARTAN study received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. Patient baseline demographic and disease characteristics were well balanced between the groups, and there were no significant differences. The median treatment duration was 16.9 months in the ERLEADA group and 11.2 months in the placebo group.²

Breast disorder TEAEs reported in the SPARTAN study are summarized in Table: Breast Disorder Treatment-Emergent Adverse Events in the Phase 3 SPARTAN Study. AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.¹

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 TITAN Study in Patients with mCSPC

The TITAN study evaluated the efficacy and safety of ERLEADA in patients with mCSPC (N=1052). Patients were randomized 1:1 to receive either ERLEADA 240 mg PO QD (n=525) or placebo QD (n=527).³ All patients in the TITAN study received a concomitant GnRH analog or had a bilateral orchiectomy.⁶ Patient baseline demographic and disease characteristics were well balanced, and there were no substantial differences between groups. Based on the data from the primary analysis, the independent data and safety monitoring committee unanimously recommended unblinding the study and offering patients assigned to the placebo arm the option to receive ERLEADA (crossover group; n=208).⁴ 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.⁴

Breast disorder TEAEs reported in the TITAN study are summarized in Table: Breast Disorder Treatment-Emergent Adverse Events in the Phase 3 TITAN Study. AEs were graded according to the NCI CTCAE Version 4.0.3.³

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 21 August 2024. Summarized in this response are relevant data limited to the phase 3 SPARTAN study in patients with nmCRPC and phase 3 TITAN study in patients with mCSPC.