SUMMARY  

• Prospective Studies
  • PANTHER study (NCT03098836): efficacy results have been reported for this ongoing, phase 2 study evaluating the use of ERLEADA and abiraterone acetate plus prednisone (AAP) in Black (n=43) and White (n=50) patients with metastatic castration-resistant prostate cancer (mCRPC) (Table: Efficacy Outcomes in Black and White Patients in the PANTHER Study).^1,2
• Subgroup Analysis
  • APA-RP study (NCT04523207): efficacy and safety results have been reported for a subgroup analysis of this phase 2 study, evaluating the use of adjuvant treatment of ERLEADA and androgen deprivation therapy (ADT) in treatment-naïve patients with high-risk localized prostate cancer who have undergone radical prostatectomy (RP; N=108). The confirmed biochemical recurrence (BCR)-free rate at 24 months was 100% in Black (90% confidence interval [CI], 57.9-100.0; n=15) and non-Black (90% CI, 93.1-100.0; n=93) patients.³ Safety results were not delineated according to race.
• Retrospective Studies – PSA & Other Results
  • In a retrospective study evaluating the prostate-specific antigen (PSA) response, treatment patterns, and adherence of ERLEADA in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) stratified by race, a total of 193 patients were included (n=33 Black patients [17.1%], n=138 non-Black patients [71.5%], n=22 unknown [11.4%]). At 12 months of follow-up, ≥50% decline in PSA from the most recent baseline PSA value (PSA50) response to ERLEADA in the overall, Black, and non-Black patient groups was in 86.0%, 93.1%, and 85.9% of patients, respectively.⁴
  • In a retrospective analysis to compare real-world PSA response by 6 months in Black patients with mCSPC treated with ERLEADA (n=236) vs abiraterone acetate (n=127), 65.4% vs 49.0% of patients in the ERLEADA vs abiraterone acetate cohorts had ≥90% decline in PSA from the most recent baseline PSA value (PSA90) response (weighted hazard ratio [HR], 1.66; 95% CI, 1.18-2.35; P=0.004).⁵ 
  • Another retrospective study evaluating real-world PSA response in patients with nmCRPC or metastatic castration-sensitive prostate cancer (mCSPC) who were treated with ERLEADA and stratified by race, a total of 313 patients with nmCRPC (n=56 Black patients, n=233 non-Black patients, n=24 unknown) and 260 patients with mCSPC (n=44 Black patients, n=193 non-Black patients, n=23 unknown) were included. PSA90 was observed in 66.0%, 74.4%, and 62.9% of overall, Black, and non-Black patients with nmCRPC, respectively, and 73.5%, 76.5%, and 74.7% of overall, Black, and non-Black patients with mCSPC, respectively.⁶
  • In a retrospective study evaluating clinical outcomes and treatment patterns in patients with mCSPC and nmCRPC who were treated with ERLEADA and stratified by race, a total of 589 patients (n=98 Black patients, n=424 non-Black patients, n=67 unknown) in the mCSPC cohort and 406 patients (n=74 Black patients, n=296 non-Black patients, n=36 other/unknown) in the nmCRPC cohort were included. Results for treatment persistence, progression to castration resistance, castration resistance-free survival (CRFS), metastasis-free survival (MFS), and PSA90 are summarized below.^7,8
• Additional retrospective studies evaluating the treatment patterns, disparities, and adherence of novel hormonal therapies including ERLEADA in patients with prostate cancer stratified by race (Black and non-Black patients) are available in the literature.^9-12
• In the phase 3 prospective TITAN and SPARTAN studies that evaluated the efficacy and safety of ERLEADA compared with placebo in patients with mCSPC (N=1052) and high-risk nmCRPC (N=1207), respectively, results were not delineated according to race. All patients received continuous ADT.
  • TITAN study: 10 (1.9%) patients in the ERLEADA group and 9 (1.7%) in the placebo group were Black/African American.¹³
  • SPARTAN study: 48 (6.0%) patients in the ERLEADA group and 20 (5.0%) in the placebo group were Black/African American.¹⁴

CLINICAL DATA

George et al (2024)¹ and (2023)² reported results of the ongoing PANTHER study evaluating the efficacy and safety of ERLEADA and AAP in patients with mCRPC stratified by race (Black, n=43; White, n=50).

Study Design/Methods

• Phase 2, prospective, open-label, multicenter, parallel cohort study
• All patients were treated with ERLEADA 240 mg orally (PO) once daily (QD), abiraterone acetate 1000 mg PO QD, and prednisone 5 mg PO twice daily (BID) until unacceptable toxicity, disease progression, or 2 years,¹⁵ at which point patients were switched to standard of care.
• Select inclusion criteria: mCRPC, prior docetaxel allowed in the mCSPC setting, adequate lab function, evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST)/Prostate Cancer Working Group 3 (PCWG3), self-reported race as either Black/African American or White
• Select exclusion criteria: prior treatment with an androgen receptor pathway inhibitor (ARPI), prior treatment with ketoconazole for prostate cancer >7 days
• Primary endpoint: radiographic progression-free survival (rPFS)
• Secondary endpoints: time to PSA progression, overall survival (OS), PSA response
• Exploratory endpoints: safety, correlative biomarkers of outcome by race and ancestry

Results

Patient Demographics

• Key baseline characteristics for each cohort are summarized in Table: Select Baseline Patient Characteristics.

Efficacy

• Efficacy outcomes for both cohorts are summarized in Table: Efficacy Outcomes in Black and White Patients in the PANTHER Study. In the long term efficacy analysis, the median follow-up was 56 months and 62 months for the Black and White cohort, respectively.

Safety

• Safety results were not reported.

Hafron et al (2024)³ reported efficacy results from a subgroup analysis of the modified intention-to-treat population (mITT) population. Black (n=15) patients were younger than non-Black (n=93) patients (mean age, 58.4 vs 66.3 years), with a median pre-operative PSA of 7.6 ng/dL (range, 2.2-62.7) and median baseline testosterone of 340.0 ng/dL (range, 43.0-939.0). The confirmed BCR-free rate at 24 months in Black patients was 100% (90% CI, 57.9-100.0) and 100% (90% CI, 93.1-100.0) in non-Black patients. The unconfirmed BCR-free rate at 24 months in Black and non-Black patients was 100% (90% CI, 57.9-100.0) and 98.2% (90% CI, 91.1-99.7), respectively. The time to serum testosterone recovery (>150 ng/dL) event rate was 66.7% (n=10) in Black patients and 75.3% (n=70) in non-Black patients, with an 18-month event rate of 47.6% (95% CI, 14.8-74.9) and 41.3% (95% CI, 30.6-51.6), and a 24-month event rate of not estimable and 74.0% (95% CI, 62.3-82.5), respectively. Safety results were not delineated according to race.

Lowentritt et al (2022)⁴ presented data from a retrospective study that evaluated the PSA response, treatment patterns, and adherence of ERLEADA in patients (overall and stratified by race [Black and non-Black]) with nmCRPC (N=193).

Study Design/Methods

• Retrospective, longitudinal cohort study conducted using electronic medical records from 63 urology practice sites in the United States (US).
• Patients with ≥2 ERLEADA prescription fills and ≥12 months of prior prostate cancer management were included.
• Outcomes assessed in the study included: PSA response, treatment patterns (including continuous treatment duration), adherence (medication possession ratio [MPR] and proportion of days covered [PDC]), and persistence rate.
  • Subgroup analyses were also performed to assess the outcomes among Black and non-Black (ie, White, Hispanic, and Asian) patients.
• PSA response was assessed among patients with a baseline PSA value and ≥1 follow-up PSA value.
  • PSA response was defined as ≥50% decline from the most recent PSA level assessed during the baseline period to any PSA measurement during the follow-up period.
• Bone metastasis was assessed during the entire follow-up period.
• Study outcomes were assessed from the index date (date of the first ERLEADA prescription) until a switch to another first or next-generation androgen signaling inhibitor (if prior to metastatic involvement), death, or the end of data availability (October 4, 2019), whichever occurred first.

Results

Baseline Characteristics

• The baseline patient characteristics were evaluated in the 12 months preceding the index date.
• There were 33 (17.1%) Black patients, 138 (71.5%) non-Black patients, and 22 (11.4%) patients that had an unknown racial background.
• Overall, most patients (75.6%) were between 71 and 90 years of age at the index date. Mean baseline PSA levels were 7.0 ng/mL, 10.5 ng/mL, and 5.6 ng/mL among patients in the overall (n=193), Black (n=33), and non-Black (n=138) groups, respectively. The most prevalent comorbidity was hypertension and was observed among 43 (22.3%), 9 (27.3%), and 29 (21.0%) patients in the overall, Black, and non-Black groups, respectively.

PSA Response

• PSA measurements were observed among 176 (91.2%), 29 (87.9%), and 126 (91.3%) patients in the overall, Black, and non-Black cohorts, respectively, within 6 months of the index date.
• The follow-up period included the following proportion of patients:
  • The mean number of PSA tests was 3.8 in all 3 groups.
  • The mean PSA levels in the overall, Black, and non-Black groups were 4.3, 3.2, and 4.0 ng/mL, respectively.
• At 12 months of follow-up, PSA response to ERLEADA in the overall, Black, and nonBlack groups was observed in 86.0%, 93.1%, and 85.9% of patients, respectively.
• During the entire follow-up period, bone metastasis was observed in 12 patients (overall, n=6 [3.1%]; Black, n=1 [3.0%]; non-Black, n=5 [3.6%]).

Treatment Patterns

• During the follow-up period, the mean duration of ERLEADA treatment with a treatment gap of >90 days in the overall, Black, and non-Black groups, respectively, was 259, 282, and 251 days.
• Treatment patterns are summarized in Table: Treatment Patterns of ERLEADA-Treated Patients.
• The persistence rates for patients without gaps of >90 days in the overall, Black, and non-Black groups, respectively, were 88.9%, 92.6%, and 87.0% at 6 months and 69.6%, 78.9%, and 65.7% at 12 months.

Safety

• Safety results were not reported.

Brown et al (2025)⁵ reported results from a retrospective study 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).

Study Design/Methods

• Retrospective, longitudinal causal analysis 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).
• Inverse probability of treatment weighting (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 either index treatment discontinuation, initiation of a non-index ARPI or radiopharmaceutical agent, or end of insurance, clinical activity, or data availability.

Results

Baseline Characteristics

• The baseline patient characteristics were evaluated in the 12 months preceding the index date.
• 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.

PSA Response

• Using Kaplan-Meier analysis, PSA90 response 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). PSA90 response was attained earlier in the ERLEADA cohort vs abiraterone acetate cohort as well: 3.3 months vs 9.1 months, respectively. Six months post-index PSA testing measurements were 78.4% and 76.5% in the ERLEADA and abiraterone acetate weighted cohorts, respectively.

Safety

• Safety results were not reported.

Bivins et al (2022)⁶ presented results of a retrospective study that evaluated real-world PSA responses in patients (overall and stratified by race [Black and non-Black]) with nmCRPC (N=313) or mCSPC (N=260) who were treated with ERLEADA.

Study Design/Methods

• Retrospective, longitudinal cohort study conducted using data from 69 urology practice sites in the US (study period: February 14, 2017 to March 5, 2021).
• Select inclusion criteria: ≥1 medication dispensation for ERLEADA; confirmed nmCRPC or mCSPC status on or before the index date.
• Exclusion criteria: use of any other next-generation androgen receptor inhibitor or biosynthesis inhibitor on or before the index date; initiation of ERLEADA prior to the FDA approval of the patient's specific indication; <12 months of clinical activity prior to the index date; evidence of prior radiopharmaceutical use.
• Study outcomes:
  • PSA50 and PSA90 response in patients with ≥1 PSA tests within 13 weeks before and >8 weeks after the index date.
  • PSA ≤0.2 response, the proportion of patients who achieved a decline to ≤0.2 ng/mL, in patients with a most recent baseline PSA value >0.2 ng/mL.
  • Time to PSA response was assessed among patients with ≥1 PSA tests within 13 weeks before and any time after the index date using Kaplan-Meier analysis.
• Patients were followed from the index date to the earliest of ERLEADA discontinuation (using a 90-day treatment gap to define discontinuation), initiation of a new nextgeneration androgen receptor inhibitor or biosynthesis inhibitor or use of radiopharmaceuticals, end of clinical activity (including death), or end of data availability, whichever occurred first.

Results

Baseline Characteristics

• The baseline patient characteristics were evaluated in the 12 months preceding the index date.
• In the nmCRPC cohort, there were 56 Black patients, 233 non-Black patients, and 24 patients with missing race information. Overall, the mean age was 79.0 years and 17.9% of patients were Black. The mean age among Black and non-Black patients was 77.1 and 79.4 years, respectively. Overall, the mean baseline PSA level was 9.9 ng/mL. The mean baseline PSA level among Black and non-Black patients was 15.0 and 8.6 ng/mL, respectively.
• In the mCSPC cohort, there were 44 Black patients, 193 non-Black patients, and 23 patients with missing race information. Overall, the mean age was 76.1 years and 16.9% of patients were Black. The mean age among Black and non-Black patients was 72.0 and 76.9 years, respectively. Overall, the mean baseline PSA level was 18.0 ng/mL. The mean baseline PSA level among Black and non-Black patients was 32.9 and 15.7 ng/mL, respectively.
• The baseline PSA closest in time to the index date was used for calculating the PSA response in patients with >1 baseline PSA value within 13 weeks before the index date.
• Concomitant ADT was used in 78.6% and 73.8% of patients in the nmCRPC and mCSPC cohorts, respectively.

PSA Response

• PSA response outcomes in the nmCRPC and mCSPC cohorts are presented in Table: PSA Response Outcomes in ERLEADA-treated Patients.

Safety

• Safety results were not reported.

Lowentritt et al (2024)⁷ presented data from a retrospective study that evaluated realworld treatment patterns and clinical outcomes in patients (overall and stratified by race [Black and non-Black]) with mCSPC (N=589) or nmCRPC (N=406) who were treated with ERLEADA.

Study Design/Methods

• Retrospective, longitudinal cohort study conducted using data from urology practice sites in the US.
• Select inclusion criteria: ≥1 in-office medication dispensation for ERLEADA, ≥12 months of clinical activity prior to the index date, evidence of metastatic disease prior to or on the index date (for mCSPC cohort)
• Select exclusion criteria: prior use of an androgen receptor signaling inhibitor (ARSI) before the index date, prior use of radiopharmaceuticals
• Among study outcomes were treatment persistence >60 days or >90 days by 6- and 12-months post-index and PSA90, assessed among patients with a baseline PSA <13 weeks prior to or on the index date and ≥1 post-index PSA test.⁸ 
• Patients were followed from index date to end of clinical activity or data availability (April 1, 2022).

Results

Baseline Characteristics

• Baseline patient characteristics were evaluated in the 12 months preceding the index date.
• In the mCSPC cohort, there were 98 (16.6%) Black patients, 424 (72.0%) non-Black patients, and 67 (11.4%) unknown patients. The mean age was 75.9 years (Black, 72.4 years; non-Black, 76.8 years) and the median time between metastasis and ERLEADA initiation was 1.5 months (Black, 2.2 months; non-Black, 1.5 months). Concurrent ADT use was observed among 96.3% patients overall (Black, 95.9%; non-Black, 96.0%). Overall, 81.2% patients had a baseline PSA test within 13 weeks of ERLEADA initiation with a mean (median) PSA level of 19.2 (3.4) ng/mL (Black, 22.7 [3.3] ng/mL; non-Black, 18.3 [3.1] ng/mL).
• In the nmCRPC cohort, there were 74 (18.2%) Black patients, 296 (72.9%) non-Black patients, and 36 (8.8%) other/unknown patients. The mean age was 78.8 years (Black, 76.2 years; non-Black, 79.3 years). Concurrent ADT use was observed among 92.1% patients overall (Black, 93.2%; non-Black, 92.7%). Overall, 90.4% patients had a baseline PSA test within 13 weeks of ERLEADA initiation with a mean (median) PSA level of 9.0 (3.6) ng/mL (Black, 13.7 [5.5] ng/mL; non-Black, 7.6 [3.3] ng/mL).

Efficacy

• Treatment persistence results are presented in Table: Treatment Outcomes in ERLEADA-treated Patients with mCSPC and nmCRPC.
• Among patients with mCSPC, overall progression to castration-resistant rates were 6.5% at 6 months (Black, 2.7%; non-Black, 7.0%), 20.9% at 12 months (Black, 23.7%; non-Black, 19.5%), and 33.5% at 24 months (Black, 31.7%; non-Black, 33.3%). Overall CRFS rates were 91.5% at 6 months (Black, 94.6%; non-Black, 90.8%), 76.2% at 12 months (Black, 74.2%; non-Black, 76.9%), and 62.0% at 24 months (Black, 63.3%; non-Black, 63.1%).⁷ At 12 months of follow-up, PSA90 was observed in 72.3%, 73.1%, and 70.8% of overall, Black, and non-Black patients and the median time to PSA response was 3.23 months, 3.77 months, and 3.13 months, respectively.⁸ 
• In patients with nmCRPC, overall MFS rates were 95.4% at 6 months (Black, 93.0%; non-Black, 96.0%), 89.7% at 12 months (Black, 88.7%; non-Black, 89.9%), and 75.4% at 24 months (Black, 76.6%; non-Black, 75.1%). Median time to MFS, progression to castration-resistance, and CRFS were not reached in any group.
• In the mCSPC cohort, overall 476 (80.8%) patients had ≥1 on-treatment PSA test (Black, 75 [76.5%]; non-Black, 346 [81.6%]), and 472 (99.2%) patients had their first PSA test within 6 months following initiation of treatment with ERLEADA. The mean (median) number of on-treatment PSA tests per year was 4.3 (3.8) overall (Black, 4.1 [3.6]; non-Black, 4.3 [3.9]).⁸ 

Safety

• Safety results were not 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 13 February 2025. Summarized in this response are relevant data limited to studies of ERLEADA with stratified results available for Black or African American patients.