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Clinical Trial
. 2024 Nov;13(21):e70029.
doi: 10.1002/cam4.70029.

Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis

Motohide Uemura  1 , Hiroaki Kikukawa  2 , Yasuhiro Hashimoto  3 , Hiroji Uemura  4 , Atsushi Mizokami  5 , Masashi Kato  6 , Hisashi Matsushima  7 , Takeo Kosaka  8 , Motonobu Nakamura  9 , Satoshi Fukasawa  10 , Matthew R Smith  11 , Bertrand Tombal  12 , Maha Hussain  13 , Fred Saad  14 , Karim Fizazi  15 , Cora N Sternberg  16 , E David Crawford  17 , Haruka Kakiuchi  18 , Masanao Akiyama  19 , Rui Li  20 , Iris Kuss  21 , Heikki Joensuu  22 , Hiroyoshi Suzuki  23
Affiliations
Clinical Trial

Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis

Motohide Uemura et al. Cancer Med. 2024 Nov.

Abstract

Background: In the global ARASENS study (NCT02799602), darolutamide plus androgen-deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57-0.80; p < 0.0001), with a favorable safety profile in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants.

Methods: Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival.

Results: The Japanese subgroup comprised 148 patients (darolutamide 63, placebo 85). In the Japanese versus overall population, more patients were aged ≥75 years (darolutamide/placebo 35%/22% vs. 16%/17%) and had body mass index <25 kg/m2 (78%/79% vs. 46%/43%), The ECOG performance status 0 (92%/88% vs. 72%/71%), de novo mHSPC (95%/97% vs. 86%/87%), and Gleason score ≥8 (94%/92% vs. 78%/79%). Median treatment duration was 43.3/15.4 months for darolutamide/placebo. The overall survival HR for darolutamide versus placebo was 0.91 (95% CI 0.50-1.64), despite 85% of patients in the placebo group receiving subsequent life-prolonging therapy. Darolutamide prolonged time to castration-resistant prostate cancer (HR 0.31; 95% CI 0.17-0.55). Treatment-emergent adverse event incidences were generally similar between groups. Adverse events known to be associated with docetaxel (e.g., neutropenia) were more frequent in the Japanese versus overall population.

Conclusion: In conclusion, efficacy outcomes showed positive trends for darolutamide plus ADT and docetaxel in Japanese patients with mHSPC, consistent with the overall population, despite higher risk factors. The combination was well tolerated, with no new safety signals in Japanese patients.

Keywords: Japanese; darolutamide; efficacy; metastatic hormone‐sensitive prostate cancer; safety.

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Conflict of interest statement

Motohide Uemura, Hiroaki Kikukawa, Yasuhiro Hashimoto, and Hiroji Uemura have no conflict of interest; Atsushi Mizokami received fees, honoraria, and remuneration from Bayer; Masashi Kato has no conflict of interest; Hisashi Matsushima received fees and honoraria from Janssen; Takeo Kosaka, Motonobu Nakamura, and Satoshi Fukasawa have no conflict of interest; Matthew R. Smith received fees, honoraria, and remuneration from Bayer; Bertrand Tombal received fees, honoraria, and remuneration from Astellas, Bayer, Janssen, and Sanofi; Maha Hussain received fees and honoraria from Astellas and Bayer, and research funds paid to her institution from Bayer; Fred Saad received fees and honoraria from Astellas, Bayer, Janssen, and Sanofi, and research funding paid to his institution from Astellas, Bayer, Janssen, and Sanofi; Karim Fizazi received fees and honoraria from Astellas, Bayer, Janssen, and Sanofi; Cora N. Sternberg received fees and honoraria from Astellas and Bayer; E. David Crawford received fees, honoraria, and remuneration from Bayer; Haruka Kakiuchi, Masanao Akiyama, Rui Li, and Iris Kuss received remuneration from Bayer (employees); Heikki Joensuu received remuneration from Orion Pharma, is Chair of the Scientific Advisory Board of Neutron Therapeutics, and owns stock in Orion Pharma and Sartar Therapeutics; Hiroyoshi Suzuki received fees, honoraria, and remuneration from Bayer and Sanofi. The study was designed under the responsibility of Bayer and Orion Pharma, in conjunction with the protocol steering committee; the study was funded by Bayer and Orion Pharma; darolutamide was provided by Bayer; Bayer collected and analyzed the data and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication.

Figures

FIGURE 1
FIGURE 1
Overall survival in (A) the Japanese subgroup and (B) the overall population. aHR stratified by extent of disease (M1a vs. M1b vs. M1c) and ALP level (< vs. ≥ ULN). Part (B) is from the New England Journal of Medicine, Smith MR, Hussain M, Saad F, et al., Darolutamide and Survival in Metastatic, Hormone‐Sensitive Prostate Cancer, Volume 386, Pages 1132–1142 Copyright © 2022 Massachusetts Medical Society. Reprinted with permission. NE, not estimable.
FIGURE 2
FIGURE 2
Time to CRPC in (A) the Japanese subgroup and (B) the overall population. aHR stratified by extent of disease (M1a vs. M1b vs. M1c) and ALP level (< vs. ≥ ULN). Part (B) is from the New England Journal of Medicine, Smith MR, Hussain M, Saad F, et al., Darolutamide and Survival in Metastatic, Hormone‐Sensitive Prostate Cancer, Volume 386, Pages 1132–1142 Copyright © 2022 Massachusetts Medical Society. Reprinted with permission.
See this image and copyright information in PMC

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