Karim Fizazi1, Christophe Massard2, Petri Bono3, Vesa Kataja4, Nicholas James5, Teuvo L Tammela6, Heikki Joensuu3, John Aspegren7, Mika Mustonen7. 1. Institut Gustave Roussy, University of Paris Sud, Villejuif, France. Electronic address: karim.fizazi@gustaveroussy.fr. 2. Institut Gustave Roussy, University of Paris Sud, Villejuif, France. 3. Comprehensive Cancer Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. 4. Kuopio University Hospital, Kuopio, Finland. 5. Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 6. Tampere University Hospital, Tampere, Finland. 7. Orion Corporation, Orion Pharma, Espoo, Finland.
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 previouschemotherapy 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 200-1800mg. 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.
RCT Entities:
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 200-1800mg. 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.
Authors: Emmanuel S Antonarakis; Andrew J Armstrong; Jun Luo; Changxue Lu; Landon C Brown Journal: Prostate Cancer Prostatic Dis Date: 2020-03-05 Impact factor: 5.554
Authors: Keiichiro Mori; Hadi Mostafaei; Benjamin Pradere; Reza Sari Motlagh; Fahad Quhal; Ekaterina Laukhtina; Victor M Schuettfort; Mohammad Abufaraj; Pierre I Karakiewicz; Takahiro Kimura; Shin Egawa; Shahrokh F Shariat Journal: Int J Clin Oncol Date: 2020-09-14 Impact factor: 3.402