TY - JOUR
T1 - Efficacy and safety of darolutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer
T2 - a sub-group analysis of the phase III ARAMIS trial
AU - Uemura, Hiroji
AU - Matsushima, Hisashi
AU - Kobayashi, Kazuki
AU - Mizusawa, Hiroya
AU - Nishimatsu, Hiroaki
AU - Fizazi, Karim
AU - Smith, Matthew
AU - Shore, Neal
AU - Tammela, Teuvo
AU - Tabata, Ken ichi
AU - Matsubara, Nobuaki
AU - Iinuma, Masahiro
AU - Uemura, Hirotsugu
AU - Oya, Mototsugu
AU - Momma, Tetsuo
AU - Kawakita, Mutsushi
AU - Fukasawa, Satoshi
AU - Kobayashi, Tadahiro
AU - Kuss, Iris
AU - Le Berre, Marie Aude
AU - Snapir, Amir
AU - Sarapohja, Toni
AU - Suzuki, Kazuhiro
N1 - Funding Information:
This study was funded by Bayer AG and Orion Pharma. The authors would like to thank the patients, their families, and all investigators involved in this study. Medical writing support, including assisting authors with the development of the outline and initial draft and incorporation of comments was provided by Charlotte Simpson, PhD, and editorial support, including fact checking, referencing, figure preparation, formatting, proofreading, and submission was provided by Annabel Ola, MSc, both of Scion, London, UK, supported by Bayer AG according to Good Publication Practice guidelines ( Link ). The Sponsor was involved in the study design, collection, analysis, and interpretation of data, as well as data checking of information provided in the manuscript. However, the ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors.
Funding Information:
Hiroji Uemura has received honoraria from Bayer, Janssen, Astellas, Takeda, and AstraZeneca, and research funding from Astellas and Takeda. Hisashi Matsushima, Kazuki Kobayashi, Hiroya Mizusawa, Hiroaki Nishimatsu, Masahiro Iinuma, Tetsuo Momma, Satoshi Fukasawa, and Tadahiro Kobayashi report no conflicts of interest. Karim Fizazi has received honoraria from, and acted as a consultant for Janssen, Bayer, Astellas, Sanofi, Orion, Curvec, AstraZeneca, Essa, Amgen, and Roche, and has received accommodation or travel expenses from Amgen and Janssen. Matthew Smith has received honoraria from and acted as a consultant for, Amgen, Astellas, Bayer, Clovis, Gilead, Janssen, Eli Lilly, Novartis, and Pfizer. Neal Shore has acted as a consultant for Bayer, Janssen, Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genentech/Roche, Myovant Sciences, Astellas Pharma, Merck, and Dendreon, and has received honoraria from Bayer, Janssen, Tolmar, Ferring, Medivation, Amgen, Pfizer, AstraZeneca, Genentech/Roche, Myovant Sciences, Astellas Pharma, Merck. Teuvo Tammela has received honoraria from Janssen, and research funding from Bayer, Lidds AB, and Astellas Pharma. Ken-ichi Tabata has received honoraria from Janssen. Nobuaki Matsubara has received honoraria from Chugai Pharmaceutical, MSD, Bayer, Sanofi, and Janssen, and research funding from Chugai Pharmaceutical, MSD, Bayer, Janssen, Astellas, AstraZeneca, Taiho Pharmaceutical, and Pfizer. Hirotsugu Uemura has acted as an advisor for Bayer, Janssen, and Sanofi; has received honoraria from Astellas, AstraZeneca, Bayer, Janssen, MSD, Sanofi, and Takeda; and has received research funding from Astellas, AstraZeneca, Janssen, Ono, Sanofi, Taiho, and Takeda. Mototsugu Oya has received honoraria from Astellas, Sanofi, Janssen, AstraZeneca, and Takeda, and research funding from Astellas. Mutsushi Kawakita has acted as an advisor for Medicaroid Corporation. Iris Kuss is an employee of and holds stocks in Bayer AG. Marie-Aude Le Berre is an employee of Bayer HealthCare. Amir Snapir was an employee of Orion Pharma and is currently an employee of PCI Biotech. Toni Sarapohja is an employee of Orion Pharma. Kazuhiro Suzuki has received honoraria from Bayer, Takeda, Astellas, Daiichi-Sankyo, AstraZeneca, Janssen, and Sanofi, and has received research funding from Takeda, Astellas, Daiichi-Sankyo.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - Background: Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Efficacy and safety of darolutamide in Japanese patients are reported here. Methods: In this randomized, double-blind, placebo-controlled phase III trial, 1509 patients with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months were randomized 2:1 to darolutamide 600 mg twice daily or matched placebo while continuing androgen deprivation therapy. The primary endpoint was MFS. Results: In Japan, 95 patients were enrolled and randomized to darolutamide (n = 62) or placebo (n = 33). At the primary analysis (cut-off date: September 3, 2018), after 20 primary end-point events had occurred, median MFS was not reached with darolutamide vs. 18.2 months with placebo (HR 0.28, 95% CI 0.11–0.70). Median OS was not reached due to limited numbers of events in both groups but favored darolutamide in the Japanese subgroup. Time to pain progression, time to PSA progression, and PSA response also favored darolutamide. Among Japanese patients randomized to darolutamide vs. placebo, incidences of treatment-emergent adverse events (TEAEs) were 85.5 vs. 63.6%, and incidences of treatment discontinuation due to TEAEs were 8.1 vs. 6.1%. Conclusions: Efficacy outcomes favored darolutamide in Japanese patients with nmCRPC, supporting the clinical benefit of darolutamide in this patient population. Darolutamide was well tolerated; however, due to the small sample size, it is impossible to conclude with certainty whether differences in the safety profile exist between Japanese and overall ARAMIS populations.
AB - Background: Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Efficacy and safety of darolutamide in Japanese patients are reported here. Methods: In this randomized, double-blind, placebo-controlled phase III trial, 1509 patients with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months were randomized 2:1 to darolutamide 600 mg twice daily or matched placebo while continuing androgen deprivation therapy. The primary endpoint was MFS. Results: In Japan, 95 patients were enrolled and randomized to darolutamide (n = 62) or placebo (n = 33). At the primary analysis (cut-off date: September 3, 2018), after 20 primary end-point events had occurred, median MFS was not reached with darolutamide vs. 18.2 months with placebo (HR 0.28, 95% CI 0.11–0.70). Median OS was not reached due to limited numbers of events in both groups but favored darolutamide in the Japanese subgroup. Time to pain progression, time to PSA progression, and PSA response also favored darolutamide. Among Japanese patients randomized to darolutamide vs. placebo, incidences of treatment-emergent adverse events (TEAEs) were 85.5 vs. 63.6%, and incidences of treatment discontinuation due to TEAEs were 8.1 vs. 6.1%. Conclusions: Efficacy outcomes favored darolutamide in Japanese patients with nmCRPC, supporting the clinical benefit of darolutamide in this patient population. Darolutamide was well tolerated; however, due to the small sample size, it is impossible to conclude with certainty whether differences in the safety profile exist between Japanese and overall ARAMIS populations.
KW - Androgen receptor inhibitor
KW - Efficacy
KW - Japanese
KW - Metastasis-free survival
KW - Nonmetastatic castration-resistant prostate cancer
KW - Safety
U2 - 10.1007/s10147-020-01824-5
DO - 10.1007/s10147-020-01824-5
M3 - Article
AN - SCOPUS:85096432471
SN - 1341-9625
VL - 26
SP - 578
EP - 590
JO - INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
JF - INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
ER -