Safety and Antitumour Activity of ODM-201 (BAY-1841788) in Chemotherapy-naïve and CYP17 Inhibitor-naïve Patients: Follow-up from the ARADES and ARAFOR Trials

Abstract 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-naive and CYP17 inhibitor (CYP17i)-naive mCRPC patients. Both trials had extended follow-up. Here we report results for chemotherapy-naive and CYP17i-naive 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-naive and CYP17i-naive 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-naive and CYP17i-naive 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.