Despite lower systemic exposure, a phase 3 randomized, open-label, clinical trial evaluating low-dose abiraterone acetate for patients with metastatic castration-resistant prostate cancer (mCRPC) found comparable survival outcomes and response rates to standard dosing.

These results will first be presented by Minit Shah, MD, Tata Memorial Centre, Mumbai, India, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting at Chicago, Illinois.

The National Comprehensive Cancer Network recently included a lower dose of abiraterone acetate (250 mg with a low-fat meal) for patients with mCRPC due to previous standard dosing of 1000 mg during fasting periods resulting in poor patient compliance.

Participants (n = 164) were randomized 1:1 to receive either low-dose abiraterone acetate with food (Arm A; n = 86) or standard-dose abiraterone acetate in the fasting state (Arm B; n = 78).

The primary end point was PSA progression-free survival (PSA-PFS) and secondary end points included PSA response rates, radiographic PFS, overall survival (OS), safety, quality of life, cost, and pharmacokinetic (pK) analysis.

Overall, the median age was 65 years (interquartile range [IQR], 60 to 71.6) and 31.7% of patients were 70 years or older. Approximately 68.3% of patients had an Eastern Cooperative Oncology Group Performance Status of 1 (ECOG-PS) and over 92% with incomes below the national average. Most patients had received prior docetaxel therapy (64%), and the median lines of prior therapy was 1 (IQR, 1). The median follow up was 18.1 months (95% confidence interval [CI], 16 to 20.2).

Response rates for PSA₃₀ (49.4% and 55.7%; P = .437) and PSA₅₀ (38.3% vs 45.7%; P = .355) were both lower in Arm A than in Arm B. However, the median PSA-PFS was higher in Arm A than in Arm B (5.7 months; 95% CI, 3.9 to 7.4 vs 3.8 months; 95% CI, 2.0 to 5.6; P = .792; hazard ratio [HR], .953; 95% CI, .663 to 1.369).  The median OS was also higher for patients in Arm A than in Arm B (18.1 months; 95% CI, 10.0 to 26.2 vs 15.1 months; 95% CI, 9.3 to 20.9; P = .969; HR, .991; 95% CI, .638 go 1.539).

Grade ≥3 toxicities were reported in 36.6% of patients in Arm A and 31.6% of patients in Arm B (P = .507).

Pharmacokinetic analysis among 58 patients demonstrated an 8-fold higher abiraterone acetate blood concentration in Arm B than in Arm (median C_max 80.5 ng/ml; range, 7.94 to 648; AUC 226 ng/ml*h; range, 27.2 to 1580 vs median C_max 10 ng/ml; range, .44 to 134; AUC 28.7 ng/ml*h; range, 0.22 to 158).

"Lower-dose abiraterone acetate 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," the researchers concluded.

Source:

Shah M, Noronha V, Menon N, et al. Lower-dose versus standard-dose abiraterone in patients with metastatic castration resistant prostate cancer: A multicentric randomized phase III non-inferiority trial. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA5078.