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
| Autor: | Heikki Joensuu, Vesa Kataja, Petri Bono, Nicholas D. James, Christophe Massard, Teuvo L.J. Tammela, John Aspegren, Mika Mustonen, Karim Fizazi |
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| Přispěvatelé: | Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, University of Tampere, Translational Cancer Biology (TCB) Research Programme, Department of Oncology, Heikki Joensuu / Principal Investigator, University Management, Clinicum, Research Programs Unit, The National Library of Finland, Research Library, HUS Comprehensive Cancer Center |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Male cytochrome P450 family 17 castration resistant prostate cancer drug safety myalgia phase 1 clinical trial very elderly diarrhea Phases of clinical research law.invention Prostate cancer 0302 clinical medicine Staphylococcus infection Randomized controlled trial law dose response advanced cancer pyrazole derivative Aged 80 and over darolutamide disease course Steroid 17-alpha-Hydroxylase hot flush clinical trial lymphedema Middle Aged cohort analysis nausea anemia backache 3. Good health Prostate-specific antigen Prostatic Neoplasms Castration-Resistant Darolutamide Treatment Outcome 030220 oncology & carcinogenesis drug withdrawal Disease Progression treatment outcome Aged headache medicine.medical_specialty gynecomastia Urology 3122 Cancers Kirurgia anestesiologia tehohoito radiologia - Surgery anesthesiology intensive care radiology drug administration antineoplastic activity prostate specific antigen Article cancer chemotherapy Drug Administration Schedule 03 medical and health sciences Internal medicine Intensive care medicine follow up Humans controlled study human arthralgia decreased appetite Adverse effect steroid 17alpha monooxygenase adult antagonists and inhibitors Aged treatment duration Dose-Response Relationship Drug business.industry treatment response Androgen Antagonists constipation clinical study medicine.disease major clinical study flatulence Surgery Clinical trial phase 2 clinical trial 030104 developmental biology multicenter study confidence interval randomized controlled trial disease exacerbation Pyrazoles antiandrogen fatigue asthenia business drug dose escalation drug tolerability |
| Popis: | 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. Extended ODM-201 therapy showed encouraging antitumour activity in both chemotherapy-naïve and chemotherapy-treated men with metastatic castration-resistant prostate cancer (CRPC). Continued treatment with ODM-201 was well tolerated, with no unexpected safety concerns, and may represent a new, effective treatment option for men with CRPC. © 2017 European Association of Urology |
| Databáze: | OpenAIRE |
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