SUMMARY

• In SPARTAN, the phase 3 study in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC; N=1207), at the final analysis of overall survival (OS), which occurred after a median follow-up of 52.0 months,¹ anemia was the only hematologic treatment-emergent adverse event (TEAE) that occurred in ≥5% in any treatment group: 10.1%, 4.3%, and 3.9% of patients in the ERLEADA, placebo, and crossover groups, respectively.² Additional hematologic TEAEs reported from the primary analysis are summarized below.
• 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,³ anemia and leukopenia were the only hematologic TEAEs that occurred in ≥5% in any treatment group: 13.2% and 5.5%, 13.7% and 4.0%, and 6.3% and 3.8% of patients in the ERLEADA, placebo, and crossover groups, respectively.⁴ Additional hematologic TEAEs reported from the primary and final analyses are summarized below. Safety results from the primary analysis were previously reported.⁵

CLINICAL DATA

Phase 3 SPARTAN Study in Patients With nmCRPC

The phase 3, randomized, double-blind, placebo-controlled SPARTAN study evaluated the efficacy and safety of ERLEADA in patients with nmCRPC (N=1207). Patients were required to have a prostate-specific antigen doubling time (PSADT) 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 (n=806) or placebo PO once daily (n=401).⁶ All patients received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. Patient baseline demographic and disease characteristics were well balanced, and there were no significant differences between groups. No patients in either group had baseline hematology laboratory values with ≥grade 3 severity.⁷ Patients were excluded if they had hemoglobin (Hb) <9.0 g/dL, platelets <100,000/µL, or absolute neutrophil count (ANC) <1500/µL.⁸ In the SPARTAN primary analysis, the median treatment duration was 16.9 months in the ERLEADA group and 11.2 months in the placebo group.^6,7 After study unblinding, patients in the placebo group were eligible for crossover into the ERLEADA group (n=76).¹

In the primary analysis, the number of patients in the safety population with hematologic TEAEs reported in the SPARTAN study, by toxicity grade, are shown in Table: Hematologic TEAEs by Toxicity Grade in the SPARTAN Study (Primary Analysis).

At the final analysis for OS, after a median follow-up of 52.0 months, anemia was the only hematologic TEAE that occurred in ≥5% in any treatment group, which occurred in 10.1%, 4.3%, and 3.9% of patients in the ERLEADA, placebo, and crossover groups, respectively.²

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 TITAN Study in Patients With mCSPC

The phase 3, randomized, double-blind, placebo-controlled 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 once daily (n=525) or placebo PO once daily (n=527).⁵ All patients received a concomitant GnRH analog or had prior bilateral orchiectomy.⁹ Patient baseline demographic and disease characteristics were well balanced, and there were no substantial differences between groups.⁵ Patients were excluded if they had Hb <9.0 g/dL, neutrophils <1.5 x 10⁹/L, or platelets <100 x 10⁹/L.⁹ In the TITAN primary analysis, the median treatment duration was 20.5 months in the ERLEADA group and 18.3 months in the placebo group.⁵ After study unblinding, patients in the placebo group were eligible for crossover into the ERLEADA group (n=208). 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 ERLEADA crossover group.³

The number of patients in the safety population with hematologic TEAEs reported at the TITAN primary analysis and at the final analysis for OS, by toxicity grade, are shown in Table: Hematologic TEAEs by Toxicity Grade in the TITAN Study.

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 24 May 2024. Summarized in this response are relevant data limited to the phase 3 SPARTAN and TITAN studies in patients with nmCRPC and mCSPC, respectively.