Low-Dose Versus Standard-Dose Abiraterone in Patients With Metastatic Castration-Resistant Prostate Cancer: A Multicenter Randomized Phase III Trial.

Abstract

Abiraterone acetate (AA) is widely used for metastatic castration-resistant prostate cancer (mCRPC), but the standard dose (1000 mg fasting) imposes challenges in resource-constrained settings due to strict fasting requirements and financial toxicity. Pharmacokinetic (PK) studies suggest that low-dose AA (250 mg with a low-fat meal) may provide comparable drug exposure, although clinical evidence remains limited. This trial compared the clinical efficacy of low-dose versus standard-dose AA. This multicenter, open-label, phase III, noninferiority trial randomly assigned patients with mCRPC, 1:1, to low-dose or standard-dose AA. The primary end point was prostate-specific antigen progression-free survival (PSA-PFS). Secondary/exploratory end points included PSA₃₀/PSA₅₀ responses (% of patients with ≥30% or ≥50% reduction in PSA), radiographic PFS, overall PFS, overall survival (OS), quality of life (QoL), and PK. Planned sample size of 314 (on the basis of a noninferiority margin of hazard ratio, 1.37) was not achieved because of slow accrual, so the noninferiority hypothesis could not be tested. A total of 164 patients were enrolled between September 2020 and January 2025 (median age 65 years; 64.0% received prior docetaxel). PSA₃₀ and PSA₅₀ responses were 50.0% and 38.5% with low-dose AA versus 55.4% (<i>P</i> = .505) and 45.9% (<i>P</i> = .350) with standard-dose AA, respectively. Median follow-up was 17.5 months. Median PSA-PFS was 5.7 months with low-dose versus 3.8 months (<i>P</i> = .830) with standard-dose AA. Median OS was 18.1 versus 15.8 months (<i>P</i> = .976). Grade ≥3 toxicities occurred in 38.3% versus 30.0% (<i>P</i> = .269), respectively. PK analyses demonstrated approximately 8-fold higher AA exposure with standard dose. QoL scores were comparable between arms. Although underpowered to prove noninferiority, low-dose AA with food yielded outcomes broadly similar to standard dosing, with maintained safety and QoL. This cost-conscious regimen may be a feasible alternative, supporting further confirmatory evaluation.