Background: ODM-201, a new androgen receptor antagonist for treatment of metastatic castration-resistant prostate cancer (mCRPC), demonstrated antitumour activity and acceptable tolerability in phase 1/2 trials.
Objective: To determine the antitumour activity and safety profile of extended treatment with ODM-201 in men with mCRPC.
Design, setting, and participants: ARADES and ARAFOR trials with ODM-201 enrolled chemotherapy-naïve and CYP17 inhibitor (CYP17i)-naïve mCRPC patients. Both trials had extended follow-up. Here we report results for chemotherapy-naïve and CYP17i-naïve patients from both trials (data cutoff October 2014 for ARADES and April 2015 for ARAFOR) after extended follow-up.
Intervention: A total of 41 chemotherapy-naïve and CYP17i-naïve patients received oral ODM-201 twice daily (total daily dose of 1200, 1400 or 1800mg).
Outcome measurements and statistical analysis: Antitumour activity was assessed in terms of prostate-specific antigen (PSA) declines and PSA/radiographic progression. Safety was assessed until disease progression and/or drug discontinuation due to any intolerable adverse event (AE).
Results and limitations: ODM-201 safety data after a median treatment time of 13.5 mo (95% confidence interval [CI] 9.7-15.6, interquartile range [IQR] 7.5-22.0) were similar to those reported in the main ARADES and ARAFOR trials. The overall AE incidence was 80.5% (n=33/41), with 58.5% (n=24/41) of patients experiencing only grade 1-2 AEs. The most common AEs were fatigue, back pain, diarrhoea, nausea, and pain in extremity. The median times to PSA and radiological progression were 12.4 mo (95% CI 6.3-18.2, IQR 5.5-22.0) and 15.3 mo (95% CI 9.5-not reached [NR], IQR 6.3-NR), respectively.
Conclusions: Extended treatment with ODM-201 (1200-1800mg/d) was well tolerated, with no new safety concerns, and provided evidence of sustained antitumour activity in chemotherapy-naïve and CYP17i-naïve patients with mCRPC.
Patient summary: Prolonged treatment with high doses of ODM-201 was well tolerated and provided long-lasting disease control in patients with mCRPC. ODM-201 represents a therapeutic treatment option for mCRPC. The ARAFOR trial (including the follow-up stage) and the follow-up component of the ARADES trial are registered with ClinicalTrials.gov as trial numbers NCT01784757 and NCT01429064.
Keywords: Androgen receptor; Androgen receptor antagonist; Metastatic castration-resistant prostate cancer; ODM-201.
Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.