Real-world STUDY

Bilen et al (2025)¹ conducted a real-world study to compare overall survival (OS) by 24 months in androgen receptor pathway inhibitor (ARPI)-naïve patients with metastatic castration-sensitive prostate cancer (mCSPC) who were newly initiated on ARPIs, ERLEADA (n=1810) or enzalutamide (n=1909).

Study Design/Methods

• Real-world, retrospective, head-to-head, causal longitudinal study
• A weighted Kaplan-Meier analysis was used to compare OS between the ERLEADA and enzalutamide cohorts at 24 months postindex (primary) and using all available follow-up data (exploratory outcome, nominal) using a weighted Cox proportional hazards model.
  • HR <1 indicated a lower death rate for the ERLEADA cohort compared with the enzalutamide cohort.
• Clinical and demographic data from Precision Point Specialty (PPS) Analytics collected as part of routine clinical care from community-based urology practices in the United States (US) were linked with administrative claims data from the Komodo Research Database (KRD) obtained from December 16, 2018 to December 31, 2023. Mortality data from KRD was used to inform the OS analysis and both databases were linked by Datavent.
  • PPS: includes prostate-specific antigen (PSA) results, dispensation information, and additional prostate cancer-specific medication and procedure data
  • KRD: includes over 320 million US patients across commercial, Medicaid, and Medicare insurers, with information on insurance eligibility, diagnoses, procedures received in inpatient and outpatient settings, and prescription fills. Mortality data are obtained from multiple third-party sources, aggregating information from national and state governments, public listings, private claims, and obituaries, capturing >90% of all deaths in oncology settings between 2018-2023 identified by the US Centers for Disease Control (CDC).
• Patients were assigned to mutually exclusive treatment cohorts based on the earliest date of the first paid pharmacy claim record in the KRD or in-office dispensation in PPS. Index dates were set as the first dispensation or paid prescription for ERLEADA or enzalutamide on or after December 16, 2019.
• Select inclusion criteria: ARPI-naïve patients with mCSPC; diagnosis code or clinical indicator for bone, nodal, or visceral metastasis without castration resistance prior to or on the index date.
• Select exclusion criteria: initiated ≥2 different ARPIs on the index date; diagnosis for another primary cancer during the baseline period; prescription in PPS for non-index ARPI; use of estrogens, immunotherapy, poly(ADP-ribose) polymerase inhibitors, radiopharmaceuticals, or etoposide; used cabazitaxel or carboplatin after docetaxel.
• Concomitant use of androgen deprivation therapy (ADT) was not required for inclusion.
• Baseline patient characteristics were evaluated 12 months pre-index and the observation period spanned from the index date until the latter of open insurance claim activity in the KRD or clinical activity in PPS, both no later than December 31, 2023.
• To account for differences in baseline characteristics between the ERLEADA and enzalutamide cohorts, inverse probability of treatment weighting (IPTW) based on propensity score was used.
  • Each patient was attributed an inverse probability of treatment weight, defined as 1/(propensity score) for the ERLEADA cohort and 1/(1-propensity score) for the enzalutamide cohort.
• Patients were not censored if they discontinued index ARPI, switched to another ARPI, initiated therapy with another advanced prostate cancer treatment, or progressed to castration resistance.
• Treatment patterns were assessed from the index date up to 24 months.
• Primary outcome: OS by 24 months postindex ARPI initiation
• This study was not designed to assess differences in safety between cohorts.

Results

Patient Characteristics

• Baseline patient characteristics were well-balanced between weighted cohorts, with standardized differences approximately <10%. 
• Patient demographics and baseline characteristics in the weighted population are included in Table: Select Demographics and Baseline Disease Characteristics.

OS

• Results are reported in Table: OS Results.
  • By 24 months postindex, patients initiated on ERLEADA had a statistically significant 23% reduction in the risk of death when compared with patients initiated on enzalutamide.
  • When evaluating OS using all available follow-up at 48 months postindex, results were consistent with OS at 24 months postindex.
  • Results were consistent in a sensitivity analysis assessing OS among a subgroup of patients treated with ADT 180 days prior to or within 180 days following the index date.

Treatment Patterns

• Results are summarized in Table: Treatment Patterns by 24 Months Postindex.

Safety results were not reported.