Lower-dose versus standard-dose abiraterone in patients with metastatic castration resistant prostate cancer: A multicentric randomized phase III non-inferiority trial.

Abstract

LBA5078 Background: Abiraterone Acetate (AbA), a novel hormonal agent, is commonly used in patients with metastatic prostate cancer. However, the standard 1000 mg dose administered in the fasting state often results in poor patient compliance. Its high cost further limits access in resource-limited settings. Recently, lower-dose AbA (250 mg with a low-fat meal) has been included in the National Comprehensive Cancer Network guidelines, however, clinical efficacy data remain limited. This study evaluates the efficacy of lower-dose AbA in our patient cohort. Methods: This randomized, open-label, multicenter, phase III non-inferiority trial enrolled patients with metastatic castration-resistant prostate cancer (mCRPC). Patients were randomized 1:1 to receive either lower-dose AbA (250 mg with a low-fat meal, Arm-A) or the standard-dose (1000 mg fasting, Arm-B). The planned sample size was 314 (80% power, 5% alpha error, 1.37 non-inferiority margin), but slow accrual led to early trial closure. The primary endpoint was PSA Progression Free Survival (PSA-PFS). Secondary endpoints were PSA response rates [PSA 30 , PSA 50 (% of patients with >30% and >50% reduction in PSA level from baseline)], radiographic PFS, overall survival (OS), QOL, cost, and pharmacokinetic (pK) analysis (Pumas v2.6). Results: The study recruited 164 patients between September 2020 and January 2025. The median age was 65 years (IQR 60.0-71.6), with 31.7% (n = 52) patients aged >70 years. The ECOG-PS was 1 in 68.3% (n = 112) of patients. A total of 92.1% (n = 151) patients had a monthly income below the national average (~₹17,000). The median number of prior treatment lines was 1 (IQR, 1), with 64.0% (n = 105) receiving prior docetaxel. Arm-A included 86 (52.4%) patients, and Arm-B had 78 (47.6%). The PSA 30 and PSA 50 response rates in Arm-A were 49.4% (n = 40/81) and 38.3% (n = 31/81), compared to 55.7% (n = 39/70, p = 0.437) and 45.7% (n = 32/70, p = 0.355) in Arm-B. The median follow-up was 18.1 months (95%CI, 16.0-20.2). The median PSA-PFS was 5.7 months (95%CI, 3.9-7.4) in Arm-A vs. 3.8 months (95%CI, 2.0-5.6) in Arm-B [p = 0.792, HR 0.953 (95%CI, 0.663-1.369)]. The median OS was 18.1 months (95%CI, 10.0-26.2) vs. 15.1 months [95%CI, 9.3-20.9; p = 0.969; HR 0.991 (95%CI, 0.638-1.539)]. Grade >3 toxicities occurred in 36.6% (n = 30/82) patients in Arm-A and 31.6% (n = 24/76) patients in Arm-B (p = 0.507). pK analysis (n = 27 Arm-A, n = 31 Arm-B) showed an 8-fold higher AbA blood concentration in Arm-B [median C max 80.5 ng/ml (range, 7.94-648), AUC 226 ng/ml*h (range, 27.2-1580)], vs. Arm-A [median C max 10 ng/ml (range, 0.44-134.0), AUC 28.7 ng/ml*h (range, 0.22-158)]. Conclusion: Lower-dose AbA shows comparable efficacy to the standard-dose despite significantly lower blood levels, making it a viable alternative. This challenges the traditional MTD-based dose determination of anti-cancer drugs. Clinical trial information: CTRI/2020/08/026967 .