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

Eur Urol Focus. 2018 Jul;4(4):547-553. doi: 10.1016/j.euf.2017.01.015. Epub 2017 Feb 14.

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-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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Androgen Receptor Antagonists / administration & dosage
  • Androgen Receptor Antagonists / adverse effects
  • Bone Neoplasms* / pathology
  • Bone Neoplasms* / secondary
  • Disease Progression
  • Drug Monitoring / methods
  • Drug-Related Side Effects and Adverse Reactions* / classification
  • Drug-Related Side Effects and Adverse Reactions* / diagnosis
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prostate / diagnostic imaging
  • Prostate-Specific Antigen / analysis*
  • Prostatic Neoplasms, Castration-Resistant* / blood
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Treatment Outcome

Substances

  • Androgen Receptor Antagonists
  • Pyrazoles
  • darolutamide
  • Prostate-Specific Antigen

Associated data

  • ClinicalTrials.gov/NCT01784757
  • ClinicalTrials.gov/NCT01429064