{"title":"Abemaciclib 联合内分泌治疗作为激素受体阳性、HER2-、高危早期乳腺癌的辅助治疗：III 期随机 monarchE 研究的 5 年中国人群分析。","authors":"Qingyuan Zhang, Kunwei Shen, Chuan-Gui Song, Quchang Ouyang, Zhenzhen Liu, Qiang Liu, Jifeng Feng, Joanne W Y Chiu, Jinhai Tang, Zefei Jiang, Ling-Ming Tseng, Xiaojia Wang, Liu Yang, Chenxi Qian, Zhimin Shao","doi":"10.1177/17588359241286775","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Abemaciclib was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved globally in the adjuvant setting for high-risk hormone-receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) early breast cancer (EBC), based on the phase III monarchE trial.</p><p><strong>Objective: </strong>To report an exploratory Chinese population analysis based on the preplanned overall survival (OS) interim analysis with 5-year efficacy results of monarchE.</p><p><strong>Design and methods: </strong>Patients with HR+/HER2-, high-risk (⩾4 positive lymph nodes, or 1-3 nodes and either tumor size ⩾5 cm, histologic grade 3, or Ki-67 ⩾20%) EBC were randomized (1:1) to abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy (ET), or ET alone. This analysis included Chinese patients enrolled in mainland China, Hong Kong, and Taiwan. The primary endpoint was invasive disease-free survival (IDFS); key secondary endpoints included distant relapse-free survival (DRFS), safety, and patient-reported outcomes (PROs).</p><p><strong>Results: </strong>Overall, 501 Chinese patients were included (abemaciclib + ET, <i>n</i> = 259; ET, <i>n</i> = 242). With a median follow-up of 53 months, the addition of abemaciclib to ET resulted in improvements in IDFS (estimated 5-year IDFS rate: 85.9% vs 79.1%; hazard ratio (HR), 0.65 (95% confidence interval (CI) 0.41-1.03)) and DRFS (estimated 5-year DRFS rate: 88.4% vs 82.3%; HR, 0.65 (95% CI, 0.39-1.07)). The most common grade ⩾3 treatment-emergent adverse events in the abemaciclib + ET versus ET groups were neutropenia (24.7% vs 0.8%) and leukopenia (22.4% vs 0.4%). Generally, no clinically meaningful difference in PROs (endocrine symptoms and fatigue) was observed between groups, except for diarrhea.</p><p><strong>Conclusion: </strong>At this prespecified OS interim analysis, which provides 5-year data, the addition of abemaciclib to ET in Chinese patients with high-risk HR+, HER2- EBC was associated with sustained and clinically meaningful improvements in IDFS and DRFS, with acceptable safety and tolerability profiles and minimal impact on PROs. These results represent the first full report of a CDK4/6 inhibitor in Chinese patients with EBC and support the positive benefit-risk profile of adjuvant abemaciclib + ET in Chinese patients.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03155997 (first posted: May 16, 2017).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241286775"},"PeriodicalIF":4.3000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503738/pdf/","citationCount":"0","resultStr":"{\"title\":\"Abemaciclib combined with endocrine therapy as adjuvant treatment for hormone-receptor-positive, HER2-, high-risk early breast cancer: 5-year Chinese population analysis of the phase III randomized monarchE study.\",\"authors\":\"Qingyuan Zhang, Kunwei Shen, Chuan-Gui Song, Quchang Ouyang, Zhenzhen Liu, Qiang Liu, Jifeng Feng, Joanne W Y Chiu, Jinhai Tang, Zefei Jiang, Ling-Ming Tseng, Xiaojia Wang, Liu Yang, Chenxi Qian, Zhimin Shao\",\"doi\":\"10.1177/17588359241286775\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Abemaciclib was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved globally in the adjuvant setting for high-risk hormone-receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) early breast cancer (EBC), based on the phase III monarchE trial.</p><p><strong>Objective: </strong>To report an exploratory Chinese population analysis based on the preplanned overall survival (OS) interim analysis with 5-year efficacy results of monarchE.</p><p><strong>Design and methods: </strong>Patients with HR+/HER2-, high-risk (⩾4 positive lymph nodes, or 1-3 nodes and either tumor size ⩾5 cm, histologic grade 3, or Ki-67 ⩾20%) EBC were randomized (1:1) to abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy (ET), or ET alone. This analysis included Chinese patients enrolled in mainland China, Hong Kong, and Taiwan. The primary endpoint was invasive disease-free survival (IDFS); key secondary endpoints included distant relapse-free survival (DRFS), safety, and patient-reported outcomes (PROs).</p><p><strong>Results: </strong>Overall, 501 Chinese patients were included (abemaciclib + ET, <i>n</i> = 259; ET, <i>n</i> = 242). With a median follow-up of 53 months, the addition of abemaciclib to ET resulted in improvements in IDFS (estimated 5-year IDFS rate: 85.9% vs 79.1%; hazard ratio (HR), 0.65 (95% confidence interval (CI) 0.41-1.03)) and DRFS (estimated 5-year DRFS rate: 88.4% vs 82.3%; HR, 0.65 (95% CI, 0.39-1.07)). The most common grade ⩾3 treatment-emergent adverse events in the abemaciclib + ET versus ET groups were neutropenia (24.7% vs 0.8%) and leukopenia (22.4% vs 0.4%). Generally, no clinically meaningful difference in PROs (endocrine symptoms and fatigue) was observed between groups, except for diarrhea.</p><p><strong>Conclusion: </strong>At this prespecified OS interim analysis, which provides 5-year data, the addition of abemaciclib to ET in Chinese patients with high-risk HR+, HER2- EBC was associated with sustained and clinically meaningful improvements in IDFS and DRFS, with acceptable safety and tolerability profiles and minimal impact on PROs. These results represent the first full report of a CDK4/6 inhibitor in Chinese patients with EBC and support the positive benefit-risk profile of adjuvant abemaciclib + ET in Chinese patients.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03155997 (first posted: May 16, 2017).</p>\",\"PeriodicalId\":23053,\"journal\":{\"name\":\"Therapeutic Advances in Medical Oncology\",\"volume\":\"16 \",\"pages\":\"17588359241286775\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503738/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17588359241286775\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17588359241286775","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景基于monarchEⅢ期试验，Abemaciclib是全球首个获批用于高危激素受体阳性（HR+）/人表皮生长因子2阴性（HER2-）早期乳腺癌（EBC）辅助治疗的细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂：报告基于monarchE 5年疗效的预计划总生存期（OS）中期分析的探索性中国人群分析：将HR+/HER2-、高危（淋巴结阳性⩾4个，或1-3个淋巴结且肿瘤大小⩾5 cm、组织学分级3级或Ki-67 ⩾20%）EBC患者随机（1:1）分为阿贝单抗（150 mg，每日2次，疗程2年）+内分泌治疗（ET）或单用ET。该分析包括在中国大陆、香港和台湾注册的中国患者。主要终点是无侵袭性疾病生存期（IDFS）；关键次要终点包括无远处复发生存期（DRFS）、安全性和患者报告结果（PROs）：共纳入501名中国患者（abemaciclib + ET，n = 259；ET，n = 242）。中位随访时间为53个月，在ET基础上加用阿巴西利可改善了IDFS（估计5年IDFS率为85.9% vs 79.1%）：85.9% vs 79.1%；危险比 (HR)，0.65（95% 置信区间 (CI)，0.41-1.03））和 DRFS（估计 5 年 DRFS 率：88.4% vs 82.3%）：88.4%对82.3%；HR，0.65（95% 置信区间，0.39-1.07））。阿昔单抗+ET组与ET组相比，最常见的⩾3级治疗突发不良事件是中性粒细胞减少（24.7% vs 0.8%）和白细胞减少（22.4% vs 0.4%）。总体而言，除腹泻外，各组间在PROs（内分泌症状和疲劳）方面未观察到有临床意义的差异：此次预设的OS中期分析提供了5年的数据，在中国高危HR+、HER2- EBC患者的ET基础上加用阿巴西利，可持续改善IDFS和DRFS，且具有临床意义，安全性和耐受性均可接受，对PROs的影响极小。这些结果代表了CDK4/6抑制剂在中国EBC患者中的首次全面报道，并支持中国患者辅助治疗阿巴西利+ET的积极获益-风险特征：试验注册：ClinicalTrials.gov identifier：NCT03155997（首次发布时间：2017年5月16日）。
Abemaciclib combined with endocrine therapy as adjuvant treatment for hormone-receptor-positive, HER2-, high-risk early breast cancer: 5-year Chinese population analysis of the phase III randomized monarchE study.
Background: Abemaciclib was the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor approved globally in the adjuvant setting for high-risk hormone-receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) early breast cancer (EBC), based on the phase III monarchE trial.
Objective: To report an exploratory Chinese population analysis based on the preplanned overall survival (OS) interim analysis with 5-year efficacy results of monarchE.
Design and methods: Patients with HR+/HER2-, high-risk (⩾4 positive lymph nodes, or 1-3 nodes and either tumor size ⩾5 cm, histologic grade 3, or Ki-67 ⩾20%) EBC were randomized (1:1) to abemaciclib (150 mg twice daily for 2 years) plus endocrine therapy (ET), or ET alone. This analysis included Chinese patients enrolled in mainland China, Hong Kong, and Taiwan. The primary endpoint was invasive disease-free survival (IDFS); key secondary endpoints included distant relapse-free survival (DRFS), safety, and patient-reported outcomes (PROs).
Results: Overall, 501 Chinese patients were included (abemaciclib + ET, n = 259; ET, n = 242). With a median follow-up of 53 months, the addition of abemaciclib to ET resulted in improvements in IDFS (estimated 5-year IDFS rate: 85.9% vs 79.1%; hazard ratio (HR), 0.65 (95% confidence interval (CI) 0.41-1.03)) and DRFS (estimated 5-year DRFS rate: 88.4% vs 82.3%; HR, 0.65 (95% CI, 0.39-1.07)). The most common grade ⩾3 treatment-emergent adverse events in the abemaciclib + ET versus ET groups were neutropenia (24.7% vs 0.8%) and leukopenia (22.4% vs 0.4%). Generally, no clinically meaningful difference in PROs (endocrine symptoms and fatigue) was observed between groups, except for diarrhea.
Conclusion: At this prespecified OS interim analysis, which provides 5-year data, the addition of abemaciclib to ET in Chinese patients with high-risk HR+, HER2- EBC was associated with sustained and clinically meaningful improvements in IDFS and DRFS, with acceptable safety and tolerability profiles and minimal impact on PROs. These results represent the first full report of a CDK4/6 inhibitor in Chinese patients with EBC and support the positive benefit-risk profile of adjuvant abemaciclib + ET in Chinese patients.
Trial registration: ClinicalTrials.gov identifier: NCT03155997 (first posted: May 16, 2017).
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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