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

Karim Fizazi, Christophe Massard, P. Bono, Vesa Kataja, Nicholas James, T.L. Tammela, H. Joensuu, John Aspegren, M. Mustonen

Research output: Contribution to journalArticleScientificpeer-review

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. 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
Original languageEnglish
JournalEuropean Urology Focus
Volume3
Issue number6
Pages (from-to)606-614
Number of pages9
ISSN2405-4569
DOIs
Publication statusPublished - 2017
MoE publication typeA1 Journal article-refereed

Fields of Science

  • cytochrome P450 family 17
  • darolutamide
  • prostate specific antigen
  • antiandrogen
  • pyrazole derivative
  • steroid 17alpha monooxygenase, adult
  • advanced cancer
  • aged
  • anemia
  • antineoplastic activity
  • arthralgia
  • Article
  • asthenia
  • backache
  • cancer chemotherapy
  • castration resistant prostate cancer
  • clinical study
  • cohort analysis
  • confidence interval
  • constipation
  • controlled study
  • decreased appetite
  • diarrhea
  • disease course
  • drug dose escalation
  • drug safety
  • drug tolerability
  • drug withdrawal
  • fatigue
  • flatulence
  • follow up
  • gynecomastia
  • headache
  • hot flush
  • human
  • lymphedema
  • major clinical study
  • male
  • multicenter study
  • myalgia
  • nausea
  • phase 1 clinical trial
  • phase 2 clinical trial
  • randomized controlled trial
  • Staphylococcus infection
  • treatment duration
  • treatment response
  • very elderly
  • antagonists and inhibitors
  • clinical trial
  • disease exacerbation
  • dose response
  • drug administration
  • middle aged
  • treatment outcome, Aged
  • Aged, 80 and over
  • Androgen Antagonists
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Humans
  • Male
  • Middle Aged
  • Prostatic Neoplasms, Castration-Resistant
  • Pyrazoles
  • Steroid 17-alpha-Hydroxylase
  • Treatment Outcome
  • 3122 Cancers

Cite this

@article{a092c8042503440b9e4660d1a7a016af,
title = "Safety and Antitumour Activity of ODM-201(BAY-1841788) in Castration-resistant, CYP17 Inhibitor-na{\"i}ve 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 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)-na{\"i}ve 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-na{\"i}ve men and not reached (NR; 95{\%} CI 5.5–NR) for chemotherapy-pretreated patients; a trend for improved antitumour response was observed for chemotherapy-na{\"i}ve patients. The median time to radiographic progression was longer for chemotherapy-na{\"i}ve (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-na{\"i}ve patients. These data support further development of ODM-201 in men with CYP17i-na{\"i}ve 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-na{\"i}ve 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. {\circledC} 2017 European Association of Urology",
keywords = "cytochrome P450 family 17, darolutamide, prostate specific antigen, antiandrogen, pyrazole derivative, steroid 17alpha monooxygenase, adult, advanced cancer, aged, anemia, antineoplastic activity, arthralgia, Article, asthenia, backache, cancer chemotherapy, castration resistant prostate cancer, clinical study, cohort analysis, confidence interval, constipation, controlled study, decreased appetite, diarrhea, disease course, drug dose escalation, drug safety, drug tolerability, drug withdrawal, fatigue, flatulence, follow up, gynecomastia, headache, hot flush, human, lymphedema, major clinical study, male, multicenter study, myalgia, nausea, phase 1 clinical trial, phase 2 clinical trial, randomized controlled trial, Staphylococcus infection, treatment duration, treatment response, very elderly, antagonists and inhibitors, clinical trial, disease exacerbation, dose response, drug administration, middle aged, treatment outcome, Aged, Aged, 80 and over, Androgen Antagonists, Disease Progression, Dose-Response Relationship, Drug, Drug Administration Schedule, Humans, Male, Middle Aged, Prostatic Neoplasms, Castration-Resistant, Pyrazoles, Steroid 17-alpha-Hydroxylase, Treatment Outcome, 3122 Cancers",
author = "Karim Fizazi and Christophe Massard and P. Bono and Vesa Kataja and Nicholas James and T.L. Tammela and H. Joensuu and John Aspegren and M. Mustonen",
year = "2017",
doi = "10.1016/j.euf.2017.01.010",
language = "English",
volume = "3",
pages = "606--614",
journal = "European Urology Focus",
issn = "2405-4569",
publisher = "Elsevier Science B.V.",
number = "6",

}

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. / Fizazi, Karim; Massard, Christophe; Bono, P.; Kataja, Vesa; James, Nicholas; Tammela, T.L.; Joensuu, H.; Aspegren, John; Mustonen, M.

In: European Urology Focus, Vol. 3 , No. 6, 2017, p. 606-614.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - 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

AU - Fizazi, Karim

AU - Massard, Christophe

AU - Bono, P.

AU - Kataja, Vesa

AU - James, Nicholas

AU - Tammela, T.L.

AU - Joensuu, H.

AU - Aspegren, John

AU - Mustonen, M.

PY - 2017

Y1 - 2017

N2 - 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

AB - 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

KW - cytochrome P450 family 17

KW - darolutamide

KW - prostate specific antigen

KW - antiandrogen

KW - pyrazole derivative

KW - steroid 17alpha monooxygenase, adult

KW - advanced cancer

KW - aged

KW - anemia

KW - antineoplastic activity

KW - arthralgia

KW - Article

KW - asthenia

KW - backache

KW - cancer chemotherapy

KW - castration resistant prostate cancer

KW - clinical study

KW - cohort analysis

KW - confidence interval

KW - constipation

KW - controlled study

KW - decreased appetite

KW - diarrhea

KW - disease course

KW - drug dose escalation

KW - drug safety

KW - drug tolerability

KW - drug withdrawal

KW - fatigue

KW - flatulence

KW - follow up

KW - gynecomastia

KW - headache

KW - hot flush

KW - human

KW - lymphedema

KW - major clinical study

KW - male

KW - multicenter study

KW - myalgia

KW - nausea

KW - phase 1 clinical trial

KW - phase 2 clinical trial

KW - randomized controlled trial

KW - Staphylococcus infection

KW - treatment duration

KW - treatment response

KW - very elderly

KW - antagonists and inhibitors

KW - clinical trial

KW - disease exacerbation

KW - dose response

KW - drug administration

KW - middle aged

KW - treatment outcome, Aged

KW - Aged, 80 and over

KW - Androgen Antagonists

KW - Disease Progression

KW - Dose-Response Relationship, Drug

KW - Drug Administration Schedule

KW - Humans

KW - Male

KW - Middle Aged

KW - Prostatic Neoplasms, Castration-Resistant

KW - Pyrazoles

KW - Steroid 17-alpha-Hydroxylase

KW - Treatment Outcome

KW - 3122 Cancers

U2 - 10.1016/j.euf.2017.01.010

DO - 10.1016/j.euf.2017.01.010

M3 - Article

VL - 3

SP - 606

EP - 614

JO - European Urology Focus

JF - European Urology Focus

SN - 2405-4569

IS - 6

ER -