Low-dose versus standard-dose abiraterone in metastatic castration-resistant prostate cancer post-docetaxel: randomized controlled trial in Brazil (Dumont)

Keywords

prostate neoplasm - castration-resistant prostate neoplasm - abiraterone acetate

Background: Abiraterone acetate (AA) is an antiandrogen agent indicated for the treatment of metastatic castration-resistant prostate cancer, category 1, at dosage of 1,000 mg once a day. It must be taken on an empty stomach, 1 hour before or 2 hours after meals. Research highlights the possibility of an alternative dose of AA at a reduced dose (250mg per day) after low-fat eating, that suggests similar PSA control in relation to the usual dose.

Objective: The primary aim was to compare, between group LOW AA (250 mg with a low-fat meal) with the STD AA dose (1,000 mg fasting), the PSA decline after 12 weeks of medication use. The secondary aims were to access progression-free survival, overall survival, PSA response rate, duration of response, safety, and quality of life.

Methods: Clinical trial, randomized, conducted in the state of Rio Grande do Norte/Brazil. Enrolled participants were randomized in a 1:1 ratio to receive AA 1000 mg on an empty stomach or 250 mg with a low-fat meal (LOW). Eligible patients are over 18 years of age with CRPC, ECOG ≤1, with disease biochemical or radiological progression. Patients must have progressed on ADT and docetaxel, treated or not with local therapy (prostatectomy or local radiotherapy). Castration can be biochemical or surgical.

Results: 38 patients were accrued: 18 in the STD AA arm and 20 in the LOW AA arm. Bone metastasis was reported in 88.9% and 75% of the patients in the STD AA and LOW AA arms, respectively. At 4 weeks (T1), there was a greater effect on PSA in the LOW arm (69.54) compared with the STD arm (66.02), and non-inferiority of the LOW arm was established according to predefined criteria. A significant difference was found between PSA values at T0 and T1 within the LOW group (p-value: 0.0210). There is a difference between the means at T0 and T1 in the following items of the EORTC QLQ-PR25 questionnaire: urinary symptoms, incontinence assistance, bowel symptoms, symptoms related to hormonal treatment, sexual activity, and sexual functioning; however, these differences are not statistically significant.

Conclusion: The reduction in PSA observed in preliminary analysis suggests that LOW AA is promising, especially in low-resource settings where financial resources are limited. However, the data are preliminary, and the final analysis must have statistical significance with the pre-specified time points (T0, T1, T2, T3) to assess the non-inferiority of the 250 mg dose combined with a low-fat diet.

Corresponding author: Ana Rafaela Nascimento e Bouças (e-mail: [e-mail]).