SUMMARY  

• Dysphagia is not listed as an adverse event (AE) associated with ERLEADA treatment in local labeling.
• Dysphagia was reported in the phase 3 registrational SPARTAN and TITAN studies, in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC; N=1207) and metastatic castration-sensitive prostate cancer (mCSPC; N=1052), respectively.^1,2 During the SPARTAN study, an amendment to switch the ERLEADA treatment formulation from softgel capsules to tablets was implemented. Patients who were receiving the softgel capsules were switched to tablets (commercial formulation) and patients newly enrolled were administered the tablet formulation. In safety subanalyses, softgel capsules were also associated with a higher incidence of gastrointestinal treatment-emergent AEs (TEAEs).³ 
  • SPARTAN: at the final analysis of overall survival (OS), which occurred after a median follow-up of 52.0 months,⁴ dysphagia was reported in 1.5% of patients in the ERLEADA group, 1.0% of patients in the placebo group, and 1.3% of patients in the crossover group. The majority of dysphagia TEAEs in the ERLEADA group at primary analysis (n=10) were reported in the capsule only group (n=3) and capsule + tablet group (n=6).⁵ 
  • TITAN: at the final analysis of OS, which occurred after a median follow-up of 44.0 months,⁶ dysphagia was reported in 0.6% of patients in the ERLEADA group, 0.6% of patients in the placebo group, and 1.0% of patients in the crossover group.⁷ 
• For patients who cannot swallow tablets whole, alternate methods of administration, including dispersion of tablets and administration with food vehicles along with administration via feeding tube, are available as an option.⁸ These methods were not available at the time of the SPARTAN and TITAN studies. Please refer to local labeling for administration details.

CLINICAL DATA

Phase 3 Study in Patients With nmCRPC (SPARTAN)

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 orally at a dose of 240 mg once daily (n=806) or placebo once daily (n=401). All patients received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. After unblinding of the study, 76 (19%) patients in the placebo group received therapy with ERLEADA plus androgen deprivation therapy (crossover group).⁴ 

During the study, an amendment to switch the ERLEADA treatment formulation from softgel capsules to tablet was implemented. In an analysis of TEAEs by formulation subgroups, the incidence of gastrointestinal TEAEs was highest in patients who received softgel capsules only and lowest among patients who received tablets only; the rates were similar for the placebo and active treatment arms. Patients who were receiving the softgel capsules were switched to tablets (commercial formulation) and patients newly enrolled were administered the tablet formulation.³ 

The incidences of dysphagia reported at the SPARTAN primary analysis and the final analysis for OS are shown in Table: Dysphagia in Phase 3 SPARTAN Study. AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.^3,5 

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 Study in Patients With mCSPC (TITAN)

The TITAN study evaluated the efficacy and safety of ERLEADA in patients with mCSPC (N=1052).² Patients were randomized 1:1 to receive either ERLEADA orally at a dose of 240 mg once daily (n=525) or placebo once daily (n=527). All patients received a concomitant GnRH analog or had a prior bilateral orchiectomy.⁹ After unblinding of the study, 208 (39.5%) patients in the placebo group received therapy with ERLEADA plus androgen deprivation therapy (crossover group).⁶ 

The incidence of dysphagia reported in the TITAN primary analysis and the final analysis for OS are shown in the Table: Dysphagia in Phase 3 TITAN Study. AEs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.3.^7,10 

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 04 February 2025. Summarized in this response are relevant data limited to the phase 3 SPARTAN and TITAN studies in patients with nmCRPC and mCSPC, respectively.