Safety and Antitumour Activity of ODM-201 (BAY-1841788) in Castration-resistant, CYP17 Inhibitor-naïve Prostate Cancer: Results from Extended Follow-up of the ARADES Trial

Abstract Background Patients with castration-resistant prostate cancer (CRPC) had extended responses to the androgen receptor antagonist ODM-201, in phase 1/2 studies. Objective To evaluate the safety and antitumour activity of prolonged ODM-201 treatment in patients with CRPC. Design, setting, and...

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Published in:European urology focus 2017-12, Vol.3 (6), p.606-614
Main Authors: Fizazi, Karim, Massard, Christophe, Bono, Petri, Kataja, Vesa, James, Nicholas, Tammela, Teuvo L, Joensuu, Heikki, Aspegren, John, Mustonen, Mika
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Androgen Antagonists - administration & dosage
Androgen Antagonists - adverse effects
Androgen receptor
Androgen receptor antagonist
Antiandrogen
Disease Progression
Dose-Response Relationship, Drug
Drug Administration Schedule
Humans
Male
Middle Aged
ODM-201
Prostate cancer
Prostatic Neoplasms, Castration-Resistant - drug therapy
Pyrazoles - administration & dosage
Pyrazoles - adverse effects
Steroid 17-alpha-Hydroxylase - antagonists & inhibitors
Treatment Outcome
Urology
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Summary:Abstract Background Patients with castration-resistant prostate cancer (CRPC) had extended responses to the androgen receptor antagonist ODM-201, in phase 1/2 studies. Objective To evaluate the safety and antitumour activity of prolonged ODM-201 treatment in patients with CRPC. Design, setting, and participants The ARADES trial was a multicentre phase 1 (dose escalation) and phase 2 (dose expansion) trial; 134 patients with CRPC were stratified by previous chemotherapy to receive ODM-201. This paper reports extended follow-up in CYP17 inhibitor (CYP17i)-naïve patients. Intervention Patients ( n = 77) received oral ODM-201 twice daily at daily doses of 200–1800 mg. Outcome measurements and statistical analysis Safety, measured as the occurrence of adverse events (AEs), prostate-specific antigen (PSA), and radiographic progression. Results and limitations The safety profile of extended ODM-201 treatment (median treatment duration 8.2 mo, 95% confidence interval [CI] 5.6–11.0) was consistent with that reported at the time of the original data cutoff in the main ARADES trial, with no unexpected safety concerns over time. The majority of AEs (61.1%) were mild (grade 1); the most common AE was fatigue/asthenia (35.1% of patients), with no clear relationship to ODM-201. Median time to PSA progression was 25.2 mo (95% CI 11.3–25.2) for chemotherapy-naïve men and not reached (NR; 95% CI 5.5–NR) for chemotherapy-pretreated patients; a trend for improved antitumour response was observed for chemotherapy-naïve patients. The median time to radiographic progression was longer for chemotherapy-naïve (14.0 mo, 95% CI 8.1–33.3) than for chemotherapy-pretreated (7.2 mo, 95% CI 2.7–11.0) patients. Conclusions Prolonged exposure to ODM-201 was well tolerated, with no additional safety concerns; disease suppression was sustained, especially in chemotherapy-naïve patients. These data support further development of ODM-201 in men with CYP17i-naïve CRPC. Patient summary Extended ODM-201 therapy was well tolerated, with beneficial antitumour activity in men with advanced prostate cancer, indicating that ODM-201 may represent a new active treatment for men with CRPC. This extension trial is registered at ClinicalTrials.gov ( www.clinicaltrials.gov ) under identification number NCT01429064.
ISSN:2405-4569
2405-4569
DOI:10.1016/j.euf.2017.01.010