SUMMARY

• In a phase 2, open-label, modular, randomized, single-center study, the efficacy and safety of abiraterone acetate, prednisone, and ERLEADA treatment was evaluated in patients with metastatic castration-resistant prostate cancer (mCRPC; N=195).¹
  • The median overall survival (OS) was 46.4 months (95% confidence interval [CI],
    39.2-68.2), 41.4 months (95% CI, 33.3-49.9), and 18.7 months (95% CI, 14.3-26.3) for patients on modules 2A (abiraterone acetate with prednisone plus ERLEADA [AAPA]), 2B (AAPA plus ipilimumab), and 3 (AAPA plus cabazitaxel and carboplatin), respectively.
  • The median failure-free survival (FFS) was 18.1 months (95% CI, 14.5-23.5), 12.8 months (95% CI, 10.6-19.8), and 9.2 months (95% CI, 6.9-11.0)² for patients on modules 2A, 2B, and 3, respectively.
  • Overall, adverse events (AEs) were reported in 76% of patients (91%, 100%, and 98% of patients on modules 2A, 2B, and 3, respectively). The most commonly reported AEs (10%) included fatigue (26%), hyperglycemia (13%), decreased lymphocyte count (13%), and anemia (10%).
• STARTAR was a phase 2, prospective, multicenter, single-arm, open-label study that evaluated combined treatment of ERLEADA and androgen deprivation therapy (ADT) for 9 months with external beam radiation therapy followed by 6 cycles of adjuvant docetaxel compared to the historical controls from the STREAM study in patients with prostate-specific antigen (PSA) recurrent prostate cancer after radical prostatectomy (N=39).³
  • The 2- and 3-year progression-free survival (PFS) were 84% and 71%, respectively; this improved significantly over the 3-yr PFS of 47% in the historic control in the multimodality trial (P=0.004) and 54% in the STREAM treatment group (P=0.039).
  • The most common AEs (>30%) included hot flashes (97%), fatigue (87%), alopecia (77%), anemia (59%), dysgeusia (59%), maculopapular rash (54%), diarrhea (44%), urinary frequency (44%), nausea (41%), insomnia (38%), urinary urgency (36%), paresthesia (36%), dyspnea (33%), pruritus (31%), and edema (31%).
• A phase 2 study (NCT03093272) evaluating the efficacy and safety of ERLEADA plus ADT in combination with docetaxel and prednisone in patients with CRPC post-abiraterone acetate (N=9) was terminated. Please refer to clinicaltrials.gov for AE results.⁴ 
• A phase 1 study evaluated the efficacy and safety of ERLEADA in combination with abiraterone acetate, prednisone, and docetaxel in patients with mCRPC (N=16).⁵ Interim results have been previously reported.⁶ 
  • PSA50 was reported in 15 (93.8%) patients; 12 (75%) patients achieved PSA90 and 4 (25%) patients had a decline of >99% from baseline.
  • At a median follow-up of 22.8 months (range, 2.8-46.6), the median PFS was not reached.
  • The 2-year PFS was 70.1% (95% CI, 32.3-89.5).
  • One dose-limiting toxicity of grade 3 hypertension was reported during dose escalation.
• Chemotherapy premedications: please refer to the approved local labeling of individual chemotherapy drugs for additional information regarding dosage and administration, including need for premedications.
  • Chemotherapy-induced nausea and vomiting, hypersensitivity reactions, and fluid retention are among numerous potential AEs associated with chemotherapy. Patients should receive pre-treatment as recommended by approved labeling, local practice guidelines, institutional practice or standards, or as clinically indicated (eg, for docetaxel, patients should receive pre-treatment oral corticosteroids to prevent hypersensitivity and fluid-retention reactions).^7,8

clinical DATA

Phase 2 Studies

Aparicio et al (2024)¹ evaluated the efficacy and safety of abiraterone acetate, prednisone, and ERLEADA treatment in a phase 2 study (NCT02703623) in patients with mCRPC (N=195).

Study Design/Methods

• Phase 2, open-label, modular, randomized, single-center study
• Module 1 (n=192): Patients received abiraterone acetate 1000 mg/day, prednisone 5 mg twice a day, and ERLEADA 240 mg/day (AAPA) in cycles of 3 weeks. After 8 weeks of treatment, patients were allocated to module 2 (satisfactory response) or module 3 (unsatisfactory response) based on whether they had PSA50 and ≤5 circulating tumor cells (CTCs) per 7.5 mL of blood.
• Module 2 (n=128): Patients with a satisfactory response were randomized to receive AAPA (arm 2A; n=64) or AAPA plus up to 4 cycles of ipilimumab 3 mg/kg intravenously (IV) (arm 2B; n=64).
• Module 3 (n=59): Patients with an unsatisfactory response received AAPA plus up to 10 cycles of cabazitaxel 25 mg/m² and carboplatin IV at area under the curve 4 (AUC 4).
• Module 4: All patients continued AAPA until criteria for treatment discontinuation were met.
• Primary endpoints: OS for modules 2 and 3, safety, and correlation between a baseline “androgen receptor (AR) responsiveness signature” with satisfactory vs unsatisfactory
  8-week serum marker decline
• Secondary endpoint: FFS

Results

Baseline Characteristics

• The median age for the overall population was 66 years (range, 43-83) and the median PSA level was 12.6 ng/mL (interquartile range [IQR], 4.2-34.4).

Efficacy

• The median OS from initial study entry for the overall population was 38.6 months (95% CI, 32.7-43.5).
• The median follow-up time was 56.8 months.
• The median OS for patients on modules 2A, 2B, and 3 was 46.4 months (95% CI,
  39.2-68.2), 41.4 months (95% CI, 33.3-49.9), and 18.7 months (95% CI, 14.3-26.3), respectively.
• The median FFS for patients on modules 2A, 2B, and 3 was 18.1 months (95% CI,
  14.5-23.5), 12.8 months (95% CI, 10.6-19.8), and 9.2 months (95% CI, 6.9-11.0)², respectively.
• Of 192 eligible patients, 154 (80.2%) underwent pretreatment metastatic biopsies. Findings included that the aggressive-variant prostate cancer molecular profile (defects in ≥2 of p53, RB1, and PTEN) was associated with unsatisfactory status.

Safety

• Overall, AEs were reported in 76% of patients (91%, 100%, and 98% of patients on modules 2A, 2B, and 3, respectively).
• The most commonly reported AEs (10%) included fatigue (26%), hyperglycemia (13%), decreased lymphocyte count (13%), and anemia (10%).
• Hypertension was reported in 30%, 25%, and 5% of patients on modules 2A, 2B, and 3, respectively.
• In module 3, febrile neutropenia was reported in 2 (3%) patients and 1 (2%) patient died due to sepsis.

STARTAR Study

STARTAR³ was a phase 2 study (NCT03311555) that evaluated combined treatment of ERLEADA and ADT for 9 months with external beam radiation therapy followed by 6 cycles of adjuvant docetaxel compared to the historical controls from the STREAM study in patients with PSA recurrent prostate cancer after radical prostatectomy (N=39).

Study Design/Methods

• Phase 2, prospective, multicenter, single-arm, open-label study
• Patients received ADT for over 9 months and ERLEADA 240 mg orally daily for approximately 36 weeks.
• Beginning week 8, external beam radiation therapy at 64.8-68 Gy was administered to the prostate bed over 6-8 weeks, followed by a 4-week washout and then docetaxel 75 mg/m² IV every 3 weeks for up to 6 cycles.
• Primary endpoint: 36-month PSA PFS
• Secondary endpoints: proportion of patients at 12, 24, and 36 months with PSA <0.1 ng/mL and testosterone recovery to >100 ng/dL; biochemical (PSA) PFS over time; PSA nadir; time to testosterone recovery; safety; and percentage of patients completing all treatments

Results

Baseline Characteristics

• The median age in the overall population and the STREAM cohort (N=38) was 64 years (IQR, 60-67 and IQR, 59-69, respectively).
• The median baseline PSA in the overall population and the STREAM cohort was 0.58 ng/mL (IQR, 0.35-1.06) and 0.4 ng/mL (0.29-0.75), respectively.

Efficacy

• The median follow-up time for patients without progression was 37 months (IQR, 36-38).
• All patients who were evaluable for the primary endpoint were alive at the time of analysis, and all the patients (100%) achieved undetectable PSA as PSA nadir on treatment.
• The 2- and 3-year PFS were 84% and 71%, respectively; this improved significantly over the 3-year PFS of 47% in the historic control in the multimodality trial and 54% in the STREAM treatment cohort (P=0.004 and P=0.039, respectively).
• Testosterone recovery was reported in 4 (11%), 31 (82%), and all 37 patients at 1 year, 2 years, and data lock, respectively.
• PSA of <0.1 ng/mL with testosterone recovery was reported in 38%, 67%, and 69% of patients at 1, 2, and 3 years, respectively.
• The median time to testosterone recovery was 15 months (95% CI, 13-17).

Safety

• The most common AEs (>30%) included hot flashes (97%), fatigue (87%), alopecia (77%), anemia (59%), dysgeusia (59%), maculopapular rash (54%), diarrhea (44%), urinary frequency (44%), nausea (41%), insomnia (38%), urinary urgency (36%), paresthesia (36%), dyspnea (33%), pruritus (31%), and edema (31%).
• The maximum hematologic grade 3-4 AEs were neutropenia (27 [69%]), including 3 febrile neutropenia events during chemotherapy.
• Serious AEs observed included febrile neutropenia (3 [8%]) and 1 (2.6%) each of: flu-like symptoms/sinus tachycardia, fever, pelvic infection, hematoma, and thromboembolism.
• Among patients who dose reduced or discontinued any part of study treatments, ERLEADA was held or dose reduced for 10 (25%) patients, with 2 (5%) patients discontinuing; docetaxel was held or dose reduced for 7 (18%) patients, with another 10 (25%) discontinuing; and radiation was held for 1 (3%) patient.
• The median number of docetaxel cycles received was 6, with 23 (62%) patients completing all 6 planned cycles of docetaxel. Some of these remaining 16 patients discontinued docetaxel early due to toxicity, but some discontinued early due to the COVID-19 pandemic out of precaution for immune suppression.

Phase 1 Study

Nauseef et al (2021)⁵ evaluated the efficacy and safety of ERLEADA in combination with abiraterone acetate, prednisone, and docetaxel in a phase 1 study (NCT02913196) in patients with mCRPC (N=16). Interim results have been previously reported.⁶ 

Study Design/Methods

• Dose escalation: Abiraterone acetate 1000 mg/day, prednisone 5 mg twice a day, and docetaxel 75 mg/m² every 3 weeks were administered with different doses of ERLEADA.
  • Cohort 1 (n=4): ERLEADA 120 mg/day
  • Cohort 2 (n=12): ERLEADA 240 mg/day
  • Following initial therapy, patients could continue the same therapy without docetaxel.
• Dose expansion: All drugs were administered at full dose.

Results

Baseline Characteristics

• The median age was 70 years and the median PSA was 3.45 ug/mL (range, 0.07-188.97).
• Metastasis was reported in bones (50%), lymph nodes (56%), lungs (6%), liver (6%), and other sites (13%).

Efficacy

• PSA50 was reported in 15 (93.8%) patients; 12 (75%) patients achieved PSA90 and 4 (25%) patients had a decline of >99% from baseline.
• At a median follow-up of 22.8 months (range, 2.8-46.6), the median radiographic PFS was not reached.
• The 2-year radiographic PFS was 70.1% (95% CI, 32.3-89.5).
• At 12 weeks, 9 of 10 evaluable patients had undetectable CTCs.

Safety

• During dose escalation, one dose-limiting toxicity of grade 3 hypertension was reported.
• In the overall study, including expansion, nonhematologic AEs were as follows: grade 3 hypertension (n=2), hyperglycemia (n=1), rash (n=1); and grade 2 hypertension (n=3), fatigue (n=3), rash (n=2), neuropathy (n=2), and nausea (n=1).
• Hematologic AEs were as follows: grade 3 anemia (n=1) and grade 4 neutropenia (n=10, 1 febrile neutropenia).

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 February 2025.