SUMMARY

• The activation of the androgen receptor signaling pathway is critical for prostate cancer tumor growth and disease progression.¹ ADT remains the mainstay in advanced prostate cancer, including for those who recur after treatment for localized disease and those with metastatic disease.^1,2
• Evidence-based guidelines recommend using ADT to maintain castrate levels of serum testosterone (<50 ng/dL) even in patients with castration-resistant prostate cancer.³
• In the phase 3 SPARTAN study evaluating the efficacy and safety of ERLEADA in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), continuous ADT with a gonadotropin-releasing hormone (GnRH) analog or surgical castration was required for all patients in order to maintain castrate levels of testosterone (<50 ng/dL).^4,5
• In the phase 3 TITAN study evaluating the efficacy and safety of ERLEADA in patients with metastatic castration-sensitive prostate cancer (mCSPC), all patients received a concomitant GnRH analog or had a bilateral orchiectomy.^6,7

Clinical data

ADT Utilization in the Phase 3 SPARTAN and TITAN Studies

Phase 3 SPARTAN Study

Smith et al (2018)⁴ evaluated the efficacy and safety of ERLEADA compared to placebo in patients with high-risk (defined as prostate-specific antigen [PSA] doubling time [PSADT] ≤10 months) nmCRPC (N=1207).

• Phase 3, randomized, double-blind, placebo-controlled, multicenter study
• Patients were randomized 2:1 to receive:
  • ERLEADA 240 mg orally once daily (n=806)
  • Placebo orally once daily (n=401)
• Continuous ADT with a GnRH analog or bilateral orchiectomy was required for patients in both treatment arms in order to maintain castrate levels of testosterone (<50 ng/dL).⁵
  • The choice of GnRH analog was at the discretion of the investigator.⁵
  • Dose and dose schedule (without interruption) were to be consistent with the prescribing information and were to be adjusted only if clinically indicated to maintain castrate concentrations of testosterone.⁵
• A total of 780 (96.8%) and 387 (96.5%) patients received therapy with a GnRH analog in the ERLEADA and placebo groups, respectively.
• A total of 47 (5.8%) and 24 (6.0%) patients had a prior bilateral orchiectomy in the ERLEADA and placebo groups, respectively.⁸

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

Chi et al (2019)⁶ evaluated the efficacy and safety of ERLEADA plus ADT compared to placebo plus ADT in patients with mCSPC (N=1052).

• Phase 3, randomized, double-blind, placebo-controlled, multicenter study
• Patients were randomized 1:1 to receive:
  • ERLEADA 240 mg orally once daily (n=525)
  • Placebo orally once daily (n=527)
• All patients received a concomitant GnRH analog or had a bilateral orchiectomy.⁷
  • The choice of GnRH analog was at the discretion of the investigator.⁷
  • Dose and frequency of administration were to be consistent with the prescribing information.⁷
• Patients who had received a GnRH agonist ≤28 days before randomization were required to take a first-generation antiandrogen for ≥14 days before randomization, and the antiandrogen must have been discontinued before randomization.
• In the ERLEADA group, 462 patients (88.2%) received prior therapy with a GnRH agonist, 56 patients (10.7%) received prior therapy with a GnRH antagonist, and 33 patients (6.3%) had prior bilateral orchiectomy.⁹
• In the placebo group, 455 patients (86.3%) received prior therapy with a GnRH agonist, 53 patients (10.1%) received prior therapy with a GnRH antagonist, and 40 patients (7.6%) had prior bilateral orchiectomy.⁹

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