Low-dose Apalutamide in Non-metastatic Castration-resistant Prostate Cancer: A Case Series

Abstract

Background/aim: Apalutamide is an androgen receptor (AR) inhibitor that has been approved for prostate cancer; however, its minimal effective dose remains unclear. This study aimed to evaluate the outcomes of low-dose apalutamide in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

Patients and methods: We conducted a retrospective chart review of patients with nmCRPC, who received ≤60 mg/day of apalutamide. Inclusion criteria were histologically confirmed prostate cancer, rising prostate-specific antigen (PSA) levels without distant metastasis at imaging, testosterone levels <0.50 mg/ml, and consent to data-sharing. The treatment start date was defined as the first dose of apalutamide treatment. PSA response was defined as a >50% decrease at week 12. Results were matched to data from a phase 1 dose-escalation study (ARN-509-001).

Results: Six patients were identified (mean age 81.1 years; range=69.6-95.0). Mean PSA level was 14.3 ng/ml (range=5.1-20.7) with a doubling time of 12.7 months (range=2.1-29.6). Disease was confined to prostate only (n=4) and prostate and pelvic nodes (n=2). ECOG performance statuses were 2 (n=2) and 0-1 (n=4). All patients showed a decrease in PSA levels at 12 weeks (binomial test, p=0.031). The time to 50% PSA decrease was 21.6 days (range=11.5-53.5). The median follow-up was 2.44 years. Five of the 6 patients were alive: 2 with undetectable PSA levels, 2 with stable disease, and 1 with an increasing PSA level that remained <2 ng/ml at 3.2 years. This data matched the dose-escalation data (ARN-509-001) that revealed 2/3 responses in patients receiving 60-90 mg/day of apalutamide.

Conclusion: Low-dose apalutamide was effective in this 6-patient case series. While awaiting new dose-response studies, we propose an apalutamide dose prescription flowchart that can be adapted for individual patients to avoid exposure to higher doses of the drug.

Keywords: ARN-509; Apalutamide; drug dose-response relationship; maximum tolerated dose; prostatic neoplasms; reduced-dose.