SUMMARY

• ERLEADA (apalutamide) is an androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. Apalutamide inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription.^1-3
• Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17-α hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. Abiraterone acetate may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition.^4-6
• No prospective, randomized, head-to-head studies comparing the efficacy and safety of ERLEADA with abiraterone acetate have been conducted.
• Results from a phase 2 study evaluating androgen deprivation therapy (ADT) plus abiraterone acetate with prednisone (AAP), ERLEADA, and ERLEADA plus AAP in patients with multiple clinical states of prostate cancer, including newly diagnosed metastatic prostate cancer, have been reported (N=128).⁷
  • Primary and secondary endpoint results at week 25 are described in Table: Primary and Secondary Endpoints at Week 25. With a median follow-up of 14 months, prostate-specific antigen (PSA) ≤0.2 ng/mL was achieved by 75.6% (95% confidence interval [CI], 59.7-87.6) of patients in the ADT plus AAP arm, 60% (95% CI, 43.3-75.1) of patients in the ERLEADA arm, and 79.5% (95% CI, 63.5-90.7) of patients in the ERLEADA plus AAP arm.⁷
  • The estimated 2-year overall survival (OS) rate was 87.9% (95% CI, 77.9-97.8) with ERLEADA, 92.7% (95% CI, 84.8-100) with ERLEADA plus AAP, and 92.5% (95% CI, 84.3-100) with AAP plus ADT (P=0.5926).⁸
  • Grade 3-4 adverse events (AEs) occurred in 31%, 21.4% and 36.4% of patients in the ADT plus AAP, ERLEADA, and ERLEADA plus AAP arms, respectively (Table: Adverse Events). Treatment-related adverse events (TRAEs) of all grades were observed in 71.4% of patients in the ADT plus AAP arm, 81% of patients in the ERLEADA arm, and 81.8% of patients in ERLEADA plus AAP arm.⁷
• Real-World, Retrospective Studies (Metastatic Castration-Sensitive Prostate Cancer) - Survival
  • Head-to-head, longitudinal study: compared OS at 24 months in patients who newly initiated ERLEADA (n=1879) vs abiraterone acetate (n=2073). By 24 months postindex, patients in the ERLEADA cohort had a 26% reduction in the risk of death compared to the abiraterone acetate cohort (88.7% vs 85.8%; hazard ratio [HR], 0.74; 95% CI, 0.59-0.93; P=0.010).⁹
  • ROMA study: unadjusted real-world survival rates were as follows for the ERLEADA (n=242) and abiraterone acetate (n=607) cohorts, respectively: 91.3% vs 88.4% by 12 months, 88% vs 82.9% by 18 months, and 85.7% vs 75.9% by 24 months. By 24 months postindex, patients in the ERLEADA cohort had a 40% lower mortality rate relative to patients initiated on abiraterone acetate (unadjusted HR, 0.60; 95% CI, 0.38-0.96; P=0.033).¹⁰
  • OASIS study: upfront treatment with ERLEADA plus ADT (n=315) compared with AAP plus ADT (n=1760) was associated with a statistically significant lower risk of death (adjusted HR, 0.72; 95% CI, 0.55-0.94; P<0.05).¹¹
  • Comparative, multicenter study: compared efficacy and safety of the androgen receptor pathway inhibitors (ARPIs) abiraterone, enzalutamide, and ERLEADA. In the matched comparison, the >99% PSA decline rate was 58% vs 72% (P=0.007) in ERLEADA- and abiraterone-treated patients, respectively. The most common AE (any grade) was liver function impairment for abiraterone (16%; n=44) and skin rash for ERLEADA (34%; n=48).¹²
• Real-World, Retrospective Studies/Analyses (Metastatic Castration-Sensitive Prostate Cancer) - PSA & Other Results
  • A retrospective, longitudinal analysis compared the real-world ≥90% decline in PSA from pretreatment levels (PSA90) in patients with de novo metastatic castration-sensitive prostate cancer (mCSPC) treated with ERLEADA (n=521) vs abiraterone acetate (n=507). Patients treated with ERLEADA were more likely to achieve a PSA90 response within 6 months of treatment compared with patients treated with abiraterone acetate (HR, 1.37; 95% CI, 1.12-1.67; P=0.002). The median time to a PSA90 response was 3.6 months vs 8.1 months, respectively.¹³
  • A retrospective analysis compared real-world PSA response by 6 months in Black patients with mCSPC treated with ERLEADA (n=236) vs abiraterone acetate (n=127). In the ERLEADA vs abiraterone acetate cohort, 65.4% vs 49% of patients, respectively, had a PSA90 response (weighted HR, 1.66; 95% CI, 1.18-2.35; P=0.004).¹⁴
  • PROMPT-2 study: patients in the ERLEADA weighted cohort were 68% more likely to achieve PSA90 response compared with the abiraterone acetate weighted cohort (HR, 1.68; 95% CI, 1.42-2; P<0.001) by 6 months postindex. The median time to PSA90 was 3.6 months vs 10.3 months, respectively.¹⁵
  • De novo study: 62.2% vs 41.6% of patients with de novo mCSPC in the ERLEADA and abiraterone acetate groups, respectively, achieved PSA90 at 6 months (HR, 1.64; 95% CI, 1.28-2.10; P<0.001). The median time to PSA90 was 3.6 months vs 10.3 months, respectively.¹⁶
  • Summary of descriptive analyses for the rates of PSA90, undetectable PSA (≤0.2 ng/mL), progression to castration resistance (CR), castration resistance-free survival (CRFS), and/or OS in patients initiated on ERLEADA or enzalutamide are summarized in Tables: Clinical Outcome Results and Table: Clinical Outcomes.^17,18
  • Summary of PSA90 response was compared between patients initiated on ERLEADA or abiraterone acetate. Results are summarized in Table: PSA90 Response Results in ERLEADA vs Abiraterone Acetate Groups.¹⁹ Additionally, PSA90 was assessed as well as undetectable PSA among patients initiated on ERLEADA or abiraterone acetate; results are summarized in Table: PSA Response Results in the ERLEADA and Abiraterone Acetate Groups.²⁰
  • A comparative study of the effectiveness of AR axis-targeted (ARAT) agents used propensity score matching to evaluate Gleason pattern 5 as a predictive factor for ARAT (including ERLEADA and abiraterone acetate) efficacy in patients with high‐risk metastatic hormone sensitive prostate cancer (mHSPC).²¹
  • A retrospective, single-center study evaluating clinical outcomes (PSA90) in chemotherapy-naïve mHSPC patients treated with ERLEADA or abiraterone acetate plus ADT has been reported.²²
• Results from an interim analysis of a long-term, real-world registry study in Japanese patients with high-risk mCSPC who received ADT alone or combined androgen blockade (cohort 1) or ADT with ERLEADA, AAP, docetaxel, or enzalutamide (cohort 2) have been reported.²³

Product Labeling

ERLEADA (apalutamide) [Prescribing Information]. Horsham, PA: Janssen Products, LP; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/ERLEADA-pi.pdf.

ZYTIGA (abiraterone acetate) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/ZYTIGA-pi.pdf.

Clinical Data

Phase 2 Study

Maluf et al (2021)⁷ reported results of a phase 2 study, LACOG-0415, that evaluated the efficacy and safety of ERLEADA, ERLEADA plus AAP, and AAP plus ADT in patients (N=128) with multiple clinical states of prostate cancer, including newly diagnosed metastatic prostate cancer (NCT02867020).

Study Design/Methods

• Phase 2, randomized, open-label, multicenter study
• Patients were randomized 1:1:1 to receive the following treatments:
  • ERLEADA 240 mg orally (PO) once daily (QD) alone
  • ERLEADA 240 mg PO QD plus abiraterone acetate 1000 mg PO QD plus prednisone 5 mg PO twice daily
  • Abiraterone acetate 1000 mg PO QD plus prednisone 5 mg PO twice daily plus ADT (goserelin 10.8 mg subcutaneously every 12 weeks)
• Patients were stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 vs 2) and metastatic disease (yes vs no).
• Patients were treated until week 25, disease progression (radiographic per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 and/or symptomatic +/- biochemical progression according to the Prostate Cancer Working Group Criteria 3), unacceptable toxicity, or consent withdrawal.
• Select inclusion criteria: locally advanced prostate cancer with positive lymph nodes, not candidates for radical surgery or radiotherapy and PSA ≥2 ng/mL; high-risk biochemical recurrence defined as PSA of ≥4 ng/mL and PSA doubling-time <10 months, or PSA ≥20 ng/mL; or mCSPC and PSA of ≥2 ng/mL; testosterone levels ≥230 ng/dL
• Select exclusion criteria: prior ADT (except in the context of local therapy with an ADT-free interval of ≥12 months prior to study entry); prostate adenocarcinoma with neuroendocrine differentiation or small cell histology; known or suspected brain or skull metastases, or leptomeningeal metastatic disease; prior hormonal therapy or chemotherapy, except if administered in the adjuvant/neoadjuvant setting for localized disease (must be completed ≥12 months before); prior radiation therapy for a primary tumor (within 3 months before study entry) or for metastases; active or asymptomatic viral hepatitis or chronic liver disease, or ascites or bleeding disorders secondary to hepatic dysfunction; surgical castration prior to study entry; impaired cardiac function; history of seizure or condition that may predispose to seizures²⁴
• Primary endpoint: proportion of patients who achieved PSA ≤0.2 ng/mL at week 25
• Secondary endpoints: PSA decline of ≥50% and ≥80% at week 25; maximum PSA decline; overall PSA change from baseline up to week 25 and up to week 52; testosterone levels during treatment; radiographic PFS; health-related quality of life (HRQoL); PSA progression; and safety

Results

Patient Characteristics

• A total of 128 patients were randomized, and 120 of these patients were evaluable for the primary endpoint.
• The baseline demographics and disease characteristics were well balanced and are presented in Table: Select Patient Baseline Characteristics.

Efficacy

• With a median follow-up of 14 months, PSA ≤0.2 ng/mL was achieved in 75.6% (95% CI, 59.7-87.6) in the ADT plus AAP arm, 60% (95% CI, 43.3-75.1) in the ERLEADA arm, and 79.5% (95% CI, 63.5-90.7) in the ERLEADA plus AAP arm at week 25.
• Primary and secondary endpoint results are described in Table: Primary and Secondary Endpoints at Week 25.
• A total of 92.3%, 80%, and 87.5% of patients without metastatic disease achieved PSA ≤0.2 ng/mL in the ADT plus AAP, ERLEADA, and ERLEADA plus AAP arms, respectively.
• PSA progression at week 25 was observed in 3 patients in the ERLEADA arm, all of whom had metastatic disease at baseline.

2-year OS and Time-to-Treatment Failure Analysis

• An additional analysis was conducted that evaluated the 2-year OS and time-to-treatment failure (TTF) outcomes from the LACOG 0415 study.⁸
  • A total of 110 patients continued treatment after week 25.
  • At the 2-year visit, 80 (62.5%) patients remained on the study treatment.
  • The estimated 2-year OS rate was 87.9% (95% CI, 77.9-97.8) with ERLEADA, 92.7% (95% CI, 84.8-100) with ERLEADA plus AAP, and 92.5% (95% CI, 84.3-100) with AAP plus ADT (P=0.5926).
  • At week 25, the 2-year OS rate was 92.9% (95% CI, 85.3-96.2) in patients with PSA ≤0.2 ng/mL and 85% (95% CI, 72.9-97.1) in patients with PSA >0.2 ng/mL (P=0.1250).
  • Median TTF was 24 months (95% CI, not estimated) with ERLEADA, 24 months (95% CI, 13-24) with ERLEADA plus AAP, and 24 months (95% CI, 23.3-24) with AAP plus ADT.

Patient-Reported HRQoL

• In an analysis evaluating patient-reported outcomes (PROs) of HRQoL, there were no clinically significant changes in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total and subscales scores from baseline to week 25 in the 3 treatment groups and no statistically significant difference between the groups in the time to FACT-P deterioration (P=0.3371).²⁵

Safety

• A summary of AEs is shown in Table: Adverse Events.
• Grade 3-4 AEs occurred in 31%, 21.4% and 36.4% of patients in the ADT plus AAP, ERLEADA, and ERLEADA plus AAP arm, respectively.
• TRAEs of all grades were observed in 71.4% of patients in the ADT plus AAP arm, 81% of patients in the ERLEADA arm, and 81.8% of patients in ERLEADA plus AAP arm.
• Treatment interruptions due to toxicity occurred in 4.8%, 9.5% and 18.2% of patients in the ADT plus AAP, ERLEADA, and ERLEADA plus AAP arms, respectively.
• A total of 9 patients discontinued therapy before week 25, of which 6 due to toxicity (ADT plus AAP arm: stroke [n=1]; ERLEADA arm: grade 3 rash [n=1]; ERLEADA plus AAP: grade 3 rash and acute renal failure [n=1], grade 3 hypertension, grade 3 rash/pruritus, grade 3 pruritus [n=1 each]).
• In the additional analysis that evaluated the 2-year OS and TTF, the reasons for treatment discontinuation included disease progression (n=8 [6.3%]), toxicity (n=10 [7.8%]), death (n=6 [4.7%]), withdrawal (n=4 [3.1%]), and other (n=19 [14.8%]).⁸

Efficacy and safety results were not delineated for patients with newly diagnosed metastatic prostate cancer.

Additional DATA

Retrospective Real-World Studies in Patients with mCSPC

Lowentritt et al (2025)⁹ conducted a real-world, retrospective, head-to-head, causal, longitudinal study to compare OS at 24 months in ARPI-naïve patients with mCSPC who were initiated on either ERLEADA (n=1879) or abiraterone acetate (n=2073). A weighted Kaplan-Meier (KM) analysis was used to compare OS between the ERLEADA and abiraterone acetate cohorts at 24 months postindex (primary) and using all available follow-up data (exploratory outcome, nominal) using weighted Cox proportional hazards models. 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 September 17, 2018 to December 31, 2023. Overall survival analyses used mortality data reported in the KRD.

Patients were assigned to mutually exclusive treatment cohorts based on the first dispensation in PPS or paid pharmacy claim in the KRD. Index dates were set as the date of treatment initiation with ERLEADA or abiraterone acetate on or after September 17, 2019. Concomitant use of ADT was not required for inclusion in either cohort, and concomitant use of prednisone was not required for inclusion in the abiraterone acetate cohort. Baseline patient characteristics were evaluated 12 months preindex date, 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 abiraterone acetate cohorts, inverse probability of treatment weighting (IPTW) based on propensity score was used.

By 24 months postindex, patients initiated on ERLEADA had a statistically significant reduction of 26% in the risk of death when compared with patients initiated on abiraterone acetate (88.7% vs 85.8%; HR, 0.74; 95% CI, 0.59-0.93; P=0.010). When evaluating OS using all available follow-up data at 48 months postindex, results were 77.3% vs 69.4% in the ERLEADA vs abiraterone acetate cohort (HR, 0.72; 95% CI, 0.59-0.88; nominal P<0.001). Median overall survival was not reached in either cohort. Results were consistent in a sensitivity analysis assessing OS among patients with a claim for ADT 180 days before or 180 days after the index date (HR, 0.78; 95% CI, 0.62-0.98; nominal P=0.035). These endpoints were not adjusted for multiple comparisons; therefore, the P-values were nominal, and statistical significance was not established. The mean (median) follow-up period was 16.8 (19.5) months vs 16.3 (19.0) months and the duration of continuous index ARPI use was 9.3 (6.6) months vs 10.7 (8.9) months in the ERLEADA vs abiraterone acetate weighted cohorts.

Bilen et al (2024)¹⁰ conducted a real-world, retrospective, longitudinal cohort study to evaluate survival among US-based patients with mCSPC who initiated ERLEADA (n=242) or abiraterone acetate (n=607) using electronic health record data from the Flatiron Metastatic Prostate Cancer Core Registry from January 2013-May 2023 (ROMA study). Concurrent use of prednisone in the abiraterone acetate cohort and concurrent ADT in both cohorts was not required for inclusion however most patients (>84%) had prior use of ADT before treatment initiation. The median time between metastasis and index treatment initiation was 2.3 months in the ERLEADA cohort and 2.5 months in the abiraterone acetate cohort.

Using KM analysis, unadjusted real-world survival rates were as follows for the ERLEADA and abiraterone acetate cohorts, respectively: 91.3% vs 88.4% by 12 months, 88% vs 82.9% by 18 months, and 85.7% vs 75.9% by 24 months. By 24 months postindex, patients in the ERLEADA cohort had a 40% lower mortality rate relative to patients initiated on abiraterone acetate (unadjusted HR, 0.60; 95% CI, 0.38-0.96; P=0.033). The median time on treatment and observation period was 11.4 months and 14.3 months in the ERLEADA cohort and 10.8 months and 14 months in the abiraterone acetate cohort.

Maughan et al (2024)¹¹ conducted a real-world, retrospective, observational cohort study to evaluate the impact of the starting treatment on short-term and long-term clinical outcomes in US patients with mHSPC (OASIS study). Patients with an mHSPC diagnosis from January 1, 2018, to June 30, 2023, in the ConcertAI database who started with any relevant upfront treatment (≥1 cycle of any ARPI, ADT, combined androgen blockade, docetaxel, radiotherapy, or prostatectomy) were included. Enrollment included 4937 patients in the comparative analysis, including upfront treatment started with ERLEADA plus ADT (n=315) and AAP plus ADT (n=1760).

At 24 months, 66% of patients in the ERLEADA plus ADT group and 59% of patients in the AAP plus ADT group were alive. Results obtained using adjusted (adjusted for age, comorbidities, BMI, and baseline PSA level) multivariate Cox regression with IPTW are shown in Table: Pair-wise Comparison of Adjusted HRs by Upfront Treatment With ERLEADA Plus ADT vs AAP Plus ADT.

Yanagisawa et al (2025)¹² conducted a real-world study to compare efficacy and safety of the ARPIs abiraterone, enzalutamide, and ERLEADA in high-risk Japanese patients (N=668) treated with ARPI-based doublet therapy between September 2015 and February 2024 were retrospectively reviewed.

Overall, 297 patients were treated with abiraterone and 142 patients were treated with ERLEADA. For intertreatment comparisons, log-rank tests were used and propensity score matching (PSM) was used while performing pairwise comparisons to minimize the effect on possible confounders.

The >99% PSA decline rate was significantly lower in ERLEADA-treated patients than in abiraterone-treated patients (58% vs 72%; P=0.007). Among patients treated with abiraterone vs ERLEADA, there were no differences in the 2‐year CRPC‐free survival (P=0.094), 3‐year OS (P=0.4), and CSS (P=0.5). The most common AE (any grade) was liver function impairment for abiraterone (16%; n=44) and skin rash for ERLEADA (34%; n=48).

Brown et al (2025)¹³ reported results from a retrospective, longitudinal cohort analysis that compared the real-world PSA90 response in patients with de novo mCSPC who were treated with ERLEADA (n=521) or abiraterone acetate (n=507).

The analysis was conducted using clinical data from the PPS Analytics Population Health Management Platform database (study period: February 1, 2017, to December 31, 2023). IPTW was applied to balance patient characteristics across the treatment cohorts. Weighted KM curves and HRs were used to compare the PSA90 response at 6 months between the treatment cohorts.

Using KM analyses, PSA90 response at 6 months was achieved by 60.2% and 47.0% of patients in the ERLEADA and abiraterone acetate cohorts, respectively (HR, 1.37; 95% CI, 1.12-1.67; P=0.002). Patients treated with ERLEADA were 37% more likely to achieve a PSA90 response within 6 months compared with those treated with abiraterone acetate. Furthermore, the median PSA90 response was attained earlier in the ERLEADA vs abiraterone acetate cohort (3.6 vs 8.1 months). During the observation period, 83.0% of patients in the ERLEADA cohort and 74.6% of patients in the abiraterone acetate cohort had ≥1 PSA measurement. Patients treated with ERLEADA had a mean of 4.4 PSA tests per year (standard deviation [SD], 3.5; median, 3.8), whereas those on abiraterone acetate had a mean of 5.1 PSA tests per year (SD, 5.0; median, 4.2).

Brown et al (2025)¹⁴ reported results from a retrospective, longitudinal causal analysis that evaluated real-world PSA90 response by 6 months in Black patients with ARPI-naïve mCSPC who were treated with ERLEADA (n=236) or abiraterone acetate (n=127).

The analysis was conducted using clinical data from >90 urology practice sites in the US linked with insurance claims data (study period: September 17, 2018, to December 31, 2023). IPTW based on propensity score was used to account for differences in baseline characteristics between both cohorts. The observation period spanned from the index date to earliest of index treatment discontinuation, initiation of a non-index ARPI or radiopharmaceutical agent or end of insurance, clinical activity, or data availability.

Concomitant prednisone was not required in the abiraterone acetate cohort and concomitant ADT was not required in either cohort. However, most patients (>86%) had prior use of ADT before treatment initiation.

Using KM analysis, PSA90 responses by 6 months were as follows for the ERLEADA and abiraterone acetate cohorts, respectively: 65.4% vs 49.0% (weighted HR, 1.66; 95% CI, 1.18-2.35; P=0.004). This result was consistent when using all available follow-up (weighted HR, 1.68; 95% CI, 1.21-2.34). Furthermore, PSA90 response was attained earlier in the ERLEADA vs abiraterone acetate cohort (3.3 vs 9.1 months). Six months post index PSA testing measurements were 78.4% and 76.5% in the ERLEADA and abiraterone acetate weighted cohorts, respectively.

Brown et al (2024)¹⁵ conducted a real-world, retrospective, longitudinal propensity score-weighted cohort study to evaluate PSA90 response by 6 months in patients with mCSPC newly initiated on ERLEADA (n=920) or abiraterone acetate (n=637) using data from the KRD from December 17, 2018-September 30, 2022 (PROMPT-2). Concurrent use of prednisone in the abiraterone acetate cohort and concurrent use of ADT in both cohorts was not required for inclusion however most patients (>86%) in the IPTW population had prior use of ADT before treatment initiation. Mean baseline PSA was 23.7 ng/mL and 25 ng/mL in the ERLEADA and abiraterone acetate weighted cohorts, respectively.

There were 82.1% of patients in the ERLEADA weighted cohort vs 74.3% of patients in the abiraterone acetate weighted cohort with a postindex PSA measurement. By 6 months postindex, patients in the ERLEADA weighted cohort were 68% more likely to achieve PSA90 response compared with the abiraterone acetate weighted cohort (HR, 1.68; 95% CI, 1.42-2; P<0.001). The same trend was observed over the entire observation period (P<0.001). At 6 months, 63.9% vs 41.7% of patients achieved PSA90 in the ERLEADA vs abiraterone acetate cohorts, with a median time to PSA90 of 3.6 months vs 10.3 months, respectively.

Brown et al (2024)¹⁶ conducted a real-world causal analysis to evaluate PSA90 response by 6 months in patients with de novo mCSPC initiated on ERLEADA (n=356) or abiraterone acetate (n=324) using data from the Komodo Health Solutions Research Database from September 17, 2019 to September 30, 2022.

A weighted KM analysis was used to compare the proportion of patients achieving a PSA90 response by 6 months and a weighted Cox proportional hazards model was used to compare the time to PSA90 response. IPTW was used to balance preindex covariates between cohorts (e.g., age, race, time from metastasis to index date, use of ADT, most recent PSA and testosterone levels).

The mean preindex PSA level was 33.3 ng/mL in both the ERLEADA and abiraterone acetate groups. By 6 months postindex, 82% of patients in the ERLEADA group and 73.5% of patients in the abiraterone acetate group had ≥1 PSA test. At 6 months, 62.2% vs 41.6% of patients achieved PSA90 in the ERLEADA vs abiraterone acetate groups (HR, 1.64; 95% CI, 1.28-2.10; P<0.001), with a median time to PSA90 of 3.6 vs 10.3 months, respectively.

Lowentritt et al (2023)¹⁷ conducted a real-world, retrospective, longitudinal cohort study to evaluate PSA outcomes and disease progression in patients with mCSPC that were initiated on ERLEADA (n=589) or abiraterone acetate (n=553). The study also included data for patients who initiated treatment with enzalutamide; however, the results for this cohort are not summarized below.

KM analyses were used to assess the rates of PSA90, PSA 0.2, progression to CR, and CRFS separately for each cohort. All analyses were descriptive and were not adjusted for potential baseline confounders. Patients were required to have ≥12 months of clinical activity prior to the index date. Concurrent use of ADT was not required for inclusion in either cohort and concurrent use of prednisone was not required for patients in the abiraterone acetate cohort. Among the exclusion criteria were prior use of an androgen receptor signaling inhibitor (ARSI) before the index date or the use of ≥2 ARSIs on the index date and prior use of any radiopharmaceuticals.

Most patients had prior use of ADT and concurrent use of ADT in the ERLEADA (90.5%, 96.3%) and abiraterone acetate (90.8%, 95.7%) cohorts, respectively. Concurrent prednisone use was observed among 94.6% patients in the abiraterone acetate cohort. Median baseline PSA was 19.2 ng/mL and 24.3 ng/mL in the ERLEADA and abiraterone acetate cohorts, respectively. The descriptive analyses are summarized in Table: Clinical Outcome Results.

Lowentritt et al (2023)¹⁸ conducted retrospective real-world analyses to describe clinical outcomes in patients with mCSPC that were initiated on ERLEADA (n=155) or abiraterone acetate (n=711) using electronic medical record data from the Flatiron Metastatic Prostate Cancer Core Registry. The study also included data for patients who initiated treatment with enzalutamide; however, the results for this cohort are not summarized below.

KM analyses were used to assess the rates of progression to CR, OS, and CRFS separately for each cohort. All analyses were descriptive and were not adjusted for potential baseline confounders. Patients were required to have ≥12 months of clinical activity prior to the index date. Concurrent use of ADT was not required for inclusion in either cohort and use of prednisone was not required for the abiraterone acetate cohort. Among the exclusion criteria were prior use of an ARSI before the index date or the use of ≥2 ARSIs on the index date, and prior use of any advanced therapy for prostate cancer (ie, chemotherapy, immunotherapy, radiopharmaceuticals, estrogens, or poly (ADP-ribose) polymerase (PARP) inhibitors).

Most patients had prior use of ADT before initiation of ERLEADA (83.2%) and abiraterone acetate (86.9%). The mean observation period was 12.7 months and 20.4 months in the ERLEADA and abiraterone acetate cohorts, respectively. The descriptive analyses are summarized in Table: Clinical Outcomes.

Clinical Outcomes¹⁸

Lowentritt et al (2023)¹⁹ conducted a real-world analysis to retrospectively compare the proportion of patients with a PSA90 by 6 months postindex and time to PSA90 response from the date of index treatment initiation in patients with mCSPC that were initiated on ERLEADA or abiraterone acetate.

IPTW based on propensity score was used to account for differences in baseline characteristics and balancing of baseline characteristics after weighting was confirmed between both cohorts. The observation period spanned from the index date to either index treatment discontinuation, initiation of a different ARSI, use of radiopharmaceuticals, end of clinical activity (eg, death), or end of data availability, whichever occurred first.

Patients were required to have ≥12 months of clinical activity prior to the index date and ≥1 PSA test during the 13 weeks prior to and including index date. Among the exclusion criteria were prior use of an ARSI before the index date or the use of ≥2 ARSIs on the index date and evidence of CR prior to or on the index date. Concomitant use of ADT was not required for inclusion and concomitant use of prednisone was not required for patients to be included in the abiraterone acetate cohort.

Before applying IPTW, a total of 364 patients treated with ERLEADA and 147 patients treated with abiraterone acetate were identified and after applying IPTW, the reweighted cohort sizes were 260 patients and 251 patients, respectively. The mean baseline PSA level was 20.4 ng/mL vs 21.1 ng/mL in the ERLEADA weighted cohort vs the abiraterone acetate weighted cohort, respectively. A total of 97.3% patients vs 99.2% patients were taking concomitant ADT in the ERLEADA and abiraterone acetate cohorts, respectively, and 93.7% of patients in the abiraterone acetate cohort were taking concomitant glucocorticoid therapy.

In the IPTW population, 77.3% of patients treated with ERLEADA and 89.2% of patients treated with abiraterone acetate had ≥1 PSA test during the observation period, with nearly all (99.6% vs 99.4%, respectively) having their first PSA test within 6 months following treatment initiation. The PSA90 response and median time to PSA90 response results were significant in the ERLEADA vs abiraterone acetate cohorts at 6 months and beyond (Table: PSA90 Response Results in ERLEADA vs Abiraterone Acetate Groups). No safety data were reported.

Pilon et al (2021)²⁰ conducted a real-world analysis to retrospectively describe PSA responses (PSA90 and undetectable PSA [PSA <0.2 ng/mL]) among patients with mCSPC who initiated treatment with ERLEADA or abiraterone acetate. The study also included data for patients who initiated treatment with enzalutamide (not summarized).

The observation period was from the index date to index treatment discontinuation, initiation of a different next-generation androgen signaling inhibitor (ASI; ERLEADA or enzalutamide) or the use of radiopharmaceuticals, end of clinical activity including death, or end of data availability, whichever occurred first. A KM analysis was used to assess the proportion of patients who achieved each PSA response outcome at 3, 6, 9, and 12 months after the index date and median time to PSA response.

Patients were required to have ≥12 months of clinical activity prior to the index date and ≥1 medication dispensation of ERLEADA, abiraterone acetate or enzalutamide. Select exclusion criteria were prior use of a next-generation ASI before the index date or the use of >1 ASI on the index date and evidence of CR prior to or on the index date. PSA responses were assessed for patients who had ≥1 PSA measurement during the 13 weeks before the index date.

Overall, 45% and 70% of patients treated with ERLEADA, respectively, and 64.7% and 78.9% of patients treated with abiraterone acetate, respectively, had a PSA test on average every 3 and 6 months. Patients achieving PSA90 and undetectable PSA responses were observed by 3 months, with the proportion increasing at 6 months postindex (Table: PSA Response Results in the ERLEADA and Abiraterone Acetate Groups). No safety data were reported.

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 July 2025. Summarized in this response are relevant data limited to patients with mCSPC. Due to methodological differences and other potential limitations including scope, timing, study designs and statistical approaches, network meta-analyses, and meta-analyses have been excluded in this response. Additional data beyond these parameters may be available in the literature.