SUMMARY

• In SPARTAN, the phase 3 study of ERLEADA in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC; N=1207), approximately 10% of patients in both treatment groups were using bone-sparing agents at baseline.¹
  • Information regarding the specific types of bone-sparing agents used has not been published.
  • At the final analysis for metastasis-free survival (MFS; following 378 events), in the subgroup of patients using concomitant bone-sparing agents, median MFS was not reached in the ERLEADA group vs 22.0 months in the placebo group (HR, 0.38; 95% CI, 0.19-0.76).¹
  • At the final analysis for overall survival (OS; following 428 events), in the subgroup of patients using concomitant bone-sparing agents, median OS was 61.5 months in the ERLEADA group vs 52.8 months in the placebo group (HR, 0.56; 95% CI, 0.311.01).² OS results, including in the subgroup of patients using concomitant bone-sparing agents, were also previously reported at the second interim analysis.³
  • In the overall population, adverse events (AEs) that occurred in ≥15% of patients in the ERLEADA group included: fatigue, hypertension, diarrhea, fall, nausea, arthralgia, weight decreased, back pain, and hot flush.²
• In TITAN, the phase 3 study of ERLEADA in patients with metastatic castration-sensitive prostate cancer (mCSPC; N=1052), the percentage of patients receiving a bone-sparing agent during the study was 17% in the ERLEADA group and 24% in the placebo group.^4,5
  • Information regarding the specific types of bone-sparing agents used has not been published.
  • Efficacy and safety were not reported for patients who did and did not receive a bone-sparing agent during the study.

CLINICAL DATA

Phase 3 SPARTAN Study - Use of Bone-Sparing Agents

In SPARTAN (NCT01946204), the randomized, double-blind, placebo-controlled, multicenter, phase 3 study of ERLEADA compared with placebo in patients with high-risk nmCRPC (N=1207) receiving continuous ADT, patients were randomized 2:1 to receive either ERLEADA 240 mg orally (PO) once daily (QD; n=806) or placebo QD (n=401).¹ Patients receiving bone loss prevention treatment with bone-sparing agents, indicated for the treatment of osteoporosis at doses and dosing schedule appropriate for the treatment of osteoporosis (eg, bisphosphonates, denosumab), were required to be on stable doses for ≥4 weeks prior to randomization.⁶ The primary endpoint of the study, MFS (defined as the time from randomization to the first detection of distant metastasis on imaging, as assessed by blinded-independent central review, or death from any cause, whichever occurred first), was evaluated for patients who did and did not receive concomitant bone-sparing agents.¹ The final analysis for the secondary endpoint of OS evaluated patients who did and did not receive concomitant bone-sparing agents.²

Results

Patient Characteristics

• A total of 82 patients (10.2%) in the ERLEADA group and 39 patients (9.7%) in the placebo group were using bone-sparing agents at baseline. Information regarding the specific types of bone-sparing agents used has not been published.¹

Efficacy Results According to Concomitant Use of Bone-Sparing Agents

Primary Analysis

• In the subgroup of patients using concomitant bone-sparing agents, median MFS was not reached in the ERLEADA group vs 22.0 months in the placebo group (HR, 0.38; 95% CI, 0.190.76).¹
• In the subgroup of patients without concomitant use of bone-sparing agents, median MFS was 40.5 months in the ERLEADA group vs 14.8 months in the placebo group (HR, 0.29; 95% CI, 0.23-0.36).¹

Final OS Analysis

• At the final analysis for OS (following 428 events), OS was the only secondary endpoint that was delineated for the subgroup of patients using concomitant bone-sparing agents.²
  • In the subgroup of patients using concomitant bone-sparing agents, the median OS was 61.5 months in the ERLEADA group vs 52.8 months in the placebo group (HR, 0.56; 95% CI, 0.31-1.01).
  • In the subgroup of patients without concomitant use of bone-sparing agents, the median OS was 73.9 months in the ERLEADA group vs 61.1 months in the placebo group (HR, 0.82; 95% CI, 0.67-1.02).

Safety

Primary Analysis

• The incidence of fracture for patients who were not receiving concomitant bone-sparing therapy at study entry was 82/722 patients (11%) in the ERLEADA group compared with 22/359 patients (6.1%) in the placebo group.⁷
  • Among patients who were receiving concomitant bone-sparing therapy at study entry, fracture occurred in 12/81 patients (15%) in the ERLEADA group and 4/39 patients (10%) in the placebo group.⁷

Final OS Analysis

• The incidence of AEs among patients using concomitant bone-sparing agents was not delineated in the final analysis.
• A summary of AEs and most frequent treatment-emergent AEs for the overall study population at the final analysis of OS is shown in Table: Adverse Events and Most Frequent Treatment-Emergent Adverse Events - Final Analysis.
  • One AE leading to death (myocardial infarction) was considered potentially related to ERLEADA.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 - Use of Bone-Sparing Agents

In TITAN (NCT02489318), the randomized, double-blind, placebo-controlled, multicenter, phase 3 study of ERLEADA compared with placebo 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).⁴ All patients in the TITAN study received a concomitant gonadotropin-releasing hormone analog or had a bilateral orchiectomy.⁸ Patients that initiated treatment with a bisphosphonate or denosumab for the management of bone metastasis <28 days prior to randomization were excluded; however, the use of these bone-sparing agents for the management of bone-related metastasis was permitted if the patients were on stable doses ≥28 days prior to randomization or such therapy was initiated following documented radiographic progression during the study. The use of bone-sparing agents at doses for prevention of osteoporosis was allowed.

A total of 17% of patients in the ERLEADA group and 24% of patients in the placebo group were receiving a bone-sparing agent during the study.⁵ Information regarding the specific types of bone-sparing agents used has not been published. Efficacy and safety were not reported for patients who did and did not receive a bone-sparing agent.

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.