SUMMARY

• Mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 3089 mL/min/1.73 m²) had no clinically relevant effects on the systemic exposure to apalutamide and N-desmethyl apalutamide.No initial dosage adjustment is necessary for patients with mild to moderate renal impairment.¹
• No data are available in patients with severe renal impairment or end-stage renal disease (eGFR ≤29 mL/min/1.73 m²).²
• In the phase 3 SPARTAN Study and TITAN Study, eligible patients were required to have adequate renal function (defined as serum creatinine ≤2x upper limit of normal
  [ULN]).^3-6
• A post-hoc analysis of the impact of patient baseline comorbidities, including renal insufficiency, on efficacy outcomes in the SPARTAN study demonstrated a significant treatment benefit in the ERLEADA group for metastasis-free survival (MFS), time to symptomatic progression, and second progression-free survival (PFS2) regardless of the presence or absence of renal insufficiency. The benefit in MFS for the ERLEADA group remained significant regardless of the number of comorbidities (0 vs 1 vs 2 vs ≥3). Incidence of treatment-emergent adverse events (AEs) was similar between patients with and without baseline comorbidities, and AEs in the ERLEADA group were not affected by comorbidities.^7,8
• There are no clinical or pharmacokinetic studies that were identified in patients receiving dialysis during treatment with ERLEADA.

Clinical dATA

Phase 3 Clinical Studies

SPARTAN Study in Patients with nmCRPC

In the phase 3 SPARTAN study, which evaluated the efficacy and safety of ERLEADA compared to placebo in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC; defined as prostate-specific antigen [PSA] doubling time [PSADT]
≤10 months) on continuous ADT (N=1207), eligible patients were required to have adequate renal function, which was defined by serum creatinine ≤2x ULN. Creatinine clearance or eGFR thresholds were not otherwise specified in the protocol.^3,4

Additional information regarding the SPARTAN study, including the clinical study report, protocol, and statistical analysis plan, can be found: 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).

Post-Hoc Analysis of Efficacy in Patients with Baseline Comorbidities

A post-hoc analysis of the impact of patient baseline comorbidities, including renal insufficiency, on MFS (primary endpoint), time to symptomatic progression (secondary endpoint), and PFS2 (exploratory endpoint) in the SPARTAN study was performed.^7,8 Additional patient baseline comorbidities including diabetes/hyperglycemia, hypertension, and cardiac disorder were analyzed; however, data related to these comorbidities were not included in this summary. Patients with and without baseline renal insufficiency and the number of comorbidities were well balanced between ERLEADA and placebo groups (refer to Table: Incidence of Patient Baseline Comorbidities and Renal Function Status in SPARTAN).

Patients with baseline comorbidities were older than patients without baseline comorbidities (median age in the ERLEADA and placebo groups: 75 years vs 69 years and 74 years vs
69 years, respectively) and had a higher Eastern Cooperative Oncology Group performance status (ECOG-PS) score (percentage of patients with ECOG-PS score of 1 in the ERLEADA and placebo groups: 25% vs 9% and 23% vs 12%, respectively).⁸ A significant treatment benefit was observed in the ERLEADA group for MFS, time to symptomatic progression, and PFS2 regardless of the presence or absence of renal insufficiency (see Tables: Impact of Patient Baseline Comorbidities and Renal Insufficiency on MFS in SPARTAN, Impact of Patient Baseline Comorbidities and Renal Insufficiency on Time to Symptomatic Progression in SPARTAN, and Impact of Patient Baseline Comorbidities and Renal Insufficiency on PFS2 in SPARTAN). The benefit in MFS for the ERLEADA group remained significant regardless of the number of comorbidities. Additionally, a significant benefit in the ERLEADA group was observed for time to symptomatic progression in patients with 0-1 comorbidities and for PFS2 in patients with 0-2 comorbidities.

The incidence of treatment-emergent AEs was similar between patients with and without baseline comorbidities (including renal insufficiency, diabetes/hyperglycemia, hypertension, and cardiac disorder), and AEs in the ERLEADA group were not affected by comorbidities (see Table: Treatment-Emergent Adverse Events by Presence of Comorbidities in SPARTAN).

TITAN Study in Patients with mCSPC

In the phase 3 TITAN study, which evaluated the efficacy and safety of ERLEADA compared to placebo in patients with metastatic castration-sensitive prostate cancer (mCSPC) on continuous ADT (N=1052), eligible patients were required to have adequate renal function, which was defined by serum creatinine ≤2x ULN. Creatinine clearance or eGFR thresholds were not otherwise specified in the protocol.^5,6

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 28 August 2024.