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
{"title":"日本转移性激素敏感性前列腺癌患者服用 Darolutamide：3期ARASENS亚组分析。","authors":"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","doi":"10.1002/cam4.70029","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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; <i>p</i> < 0.0001), with a favorable safety profile in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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/m<sup>2</sup> (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.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552649/pdf/","citationCount":"0","resultStr":"{\"title\":\"Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis\",\"authors\":\"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\",\"doi\":\"10.1002/cam4.70029\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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; <i>p</i> < 0.0001), with a favorable safety profile in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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/m<sup>2</sup> (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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":139,\"journal\":{\"name\":\"Cancer Medicine\",\"volume\":\"13 21\",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-11-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552649/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70029\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70029","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
研究背景在全球ARASENS研究（NCT02799602）中，达罗鲁胺联合雄激素剥夺疗法（ADT）和多西他赛与安慰剂联合ADT和多西他赛相比，可显著降低32.5%的死亡风险（危险比[HR]0.68；95%置信区间[CI]0.57-0.80；P 方法：患者按1:1的比例随机接受口服达罗鲁胺600毫克，每日两次或安慰剂联合ADT和多西他赛治疗：患者按1:1比例随机接受口服达罗鲁胺600毫克，每日两次或安慰剂加ADT和多西他赛治疗。主要终点是总生存期：日本亚组有148名患者（达罗鲁胺63名，安慰剂85名）。日本患者与总体患者相比，年龄≥75岁的患者较多（达罗他胺/安慰剂为35%/22% vs. 16%/17%），体重指数为2（78%/79% vs. 46%/43%），ECOG表现为0（92%/88% vs. 72%/71%），新发mHSPC（95%/97% vs. 86%/87%），Gleason评分≥8（94%/92% vs. 78%/79%）。达罗芦胺/安慰剂的中位治疗时间为43.3/15.4个月。尽管安慰剂组中有85%的患者随后接受了延长生命的治疗，但达罗他胺与安慰剂相比的总生存率为0.91（95% CI 0.50-1.64）。达罗他胺可延长罹患阉割耐药前列腺癌的时间（HR 0.31；95% CI 0.17-0.55）。各组的治疗突发不良事件发生率基本相似。已知与多西他赛相关的不良事件（如中性粒细胞减少症）在日本人群中的发生率高于总体人群：总之，尽管日本mHSPC患者的风险因素较高，但达罗鲁胺联合ADT和多西他赛的疗效结果显示出积极的趋势，与总体人群一致。日本患者对联合用药的耐受性良好，没有出现新的安全信号。
Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis
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.
期刊介绍：
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
