Darolutamide in Japanese patients with metastatic hormone‐sensitive prostate cancer: Phase 3 ARASENS subgroup analysis
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...
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Wiley
2024-11-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70029 |
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| author | Motohide Uemura Hiroaki Kikukawa Yasuhiro Hashimoto Hiroji Uemura Atsushi Mizokami Masashi Kato Hisashi Matsushima Takeo Kosaka Motonobu Nakamura Satoshi Fukasawa Matthew R. Smith Bertrand Tombal Maha Hussain Fred Saad Karim Fizazi Cora N. Sternberg E. David Crawford Haruka Kakiuchi Masanao Akiyama Rui Li Iris Kuss Heikki Joensuu Hiroyoshi Suzuki |
| author_facet | Motohide Uemura Hiroaki Kikukawa Yasuhiro Hashimoto Hiroji Uemura Atsushi Mizokami Masashi Kato Hisashi Matsushima Takeo Kosaka Motonobu Nakamura Satoshi Fukasawa Matthew R. Smith Bertrand Tombal Maha Hussain Fred Saad Karim Fizazi Cora N. Sternberg E. David Crawford Haruka Kakiuchi Masanao Akiyama Rui Li Iris Kuss Heikki Joensuu Hiroyoshi Suzuki |
| author_sort | Motohide Uemura |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1058407c6e5d4f8494ab24581515bb95 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-1058407c6e5d4f8494ab24581515bb952024-11-13T07:40:34ZengWileyCancer Medicine2045-76342024-11-011321n/an/a10.1002/cam4.70029Darolutamide in Japanese patients with metastatic hormone‐sensitive prostate cancer: Phase 3 ARASENS subgroup analysisMotohide Uemura0Hiroaki Kikukawa1Yasuhiro Hashimoto2Hiroji Uemura3Atsushi Mizokami4Masashi Kato5Hisashi Matsushima6Takeo Kosaka7Motonobu Nakamura8Satoshi Fukasawa9Matthew R. Smith10Bertrand Tombal11Maha Hussain12Fred Saad13Karim Fizazi14Cora N. Sternberg15E. David Crawford16Haruka Kakiuchi17Masanao Akiyama18Rui Li19Iris Kuss20Heikki Joensuu21Hiroyoshi Suzuki22Department of Urology Osaka University Hospital Osaka JapanDepartment of Urology National Hospital Organization Kumamoto Medical Center Kumamoto JapanDepartment of Urology Hirosaki University School of Medicine and Hospital Hirosaki JapanDepartment of Urology Yokohama City University Medical Center Yokohama JapanDepartment of Urology Kanazawa University Hospital Kanazawa JapanDepartment of Urology Nagoya University Hospital Nagoya JapanDepartment of Urology Tokyo Metropolitan Police Hospital Tokyo JapanDepartment of Urology Keio University Hospital Tokyo JapanDepartment of Urology National Hospital Organization Kyushu Cancer Center Fukuoka JapanProstate Center and Division of Urology Chiba Cancer Center Chiba JapanGenitourinary Oncology Program Massachusetts General Hospital Cancer Center and Harvard Medical School Boston Massachusetts USADivision of Urology, IREC Cliniques Universitaires Saint‐Luc, Université Catholique de Louvain Brussels BelgiumDivision of Hematology‐Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine Chicago Illinois USADepartment of Urology University of Montreal Hospital Center Montréal Québec CanadaDepartment of Cancer Medicine Institut Gustave Roussy, University of Paris–Saclay Villejuif FranceDepartment of Medicine Englander Institute for Precision Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York‐Presbyterian Hospital New York New York USADepartment of Urology University of California San Diego School of Medicine La Jolla California USABayer Yakuhin, Ltd Osaka JapanBayer Yakuhin, Ltd Tokyo JapanBayer HealthCare Pharmaceuticals Inc. Whippany New Jersey USABayer AG Berlin GermanyOrion Corporation Espoo FinlandDepartment of Urology Toho University Sakura Medical Center Sakura JapanAbstract 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.https://doi.org/10.1002/cam4.70029darolutamideefficacyJapanesemetastatic hormone‐sensitive prostate cancersafety |
| spellingShingle | Motohide Uemura Hiroaki Kikukawa Yasuhiro Hashimoto Hiroji Uemura Atsushi Mizokami Masashi Kato Hisashi Matsushima Takeo Kosaka Motonobu Nakamura Satoshi Fukasawa Matthew R. Smith Bertrand Tombal Maha Hussain Fred Saad Karim Fizazi Cora N. Sternberg E. David Crawford Haruka Kakiuchi Masanao Akiyama Rui Li Iris Kuss Heikki Joensuu Hiroyoshi Suzuki Darolutamide in Japanese patients with metastatic hormone‐sensitive prostate cancer: Phase 3 ARASENS subgroup analysis Cancer Medicine darolutamide efficacy Japanese metastatic hormone‐sensitive prostate cancer safety |
| title | Darolutamide in Japanese patients with metastatic hormone‐sensitive prostate cancer: Phase 3 ARASENS subgroup analysis |
| title_full | Darolutamide in Japanese patients with metastatic hormone‐sensitive prostate cancer: Phase 3 ARASENS subgroup analysis |
| title_fullStr | Darolutamide in Japanese patients with metastatic hormone‐sensitive prostate cancer: Phase 3 ARASENS subgroup analysis |
| title_full_unstemmed | Darolutamide in Japanese patients with metastatic hormone‐sensitive prostate cancer: Phase 3 ARASENS subgroup analysis |
| title_short | Darolutamide in Japanese patients with metastatic hormone‐sensitive prostate cancer: Phase 3 ARASENS subgroup analysis |
| title_sort | darolutamide in japanese patients with metastatic hormone sensitive prostate cancer phase 3 arasens subgroup analysis |
| topic | darolutamide efficacy Japanese metastatic hormone‐sensitive prostate cancer safety |
| url | https://doi.org/10.1002/cam4.70029 |
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