Abemaciclib Dose Escalation in Early High-Risk Breast Cancer Adjuvant Therapy (ADES)
Study on the Safety and Efficacy of Abemaciclib Dose Escalation Strategy in Adjuvant Therapy for Early High-Risk Breast Cancer
Abemaciclib combined with endocrine therapy has become one of the important adjuvant treatment regimens for patients with HR+/HER2- high-risk early breast cancer. However, adverse events such as diarrhea, fatigue, neutropenia and elevated liver enzymes are concentrated in the early stage of adjuvant therapy, which often lead to dose reduction, temporary drug interruption or even permanent discontinuation. This further affects treatment adherence, relative dose intensity (RDI) and treatment completion rate.
Findings from the TRADE study suggest that a step-up dosing strategy, initiating at a lower dose followed by gradual titration to the standard dose, combined with standardized patient education and symptomatic management, may improve early treatment tolerance, reduce the burden of partial toxicities, and increase the likelihood of patients achieving and maintaining abemaciclib 150 mg twice daily. Based on the above evidence and clinical experience, step-up dosing has been adopted by some clinicians for real-world clinical practice.
Nevertheless, existing evidence is mainly derived from non-Chinese populations. There is still a lack of systematic real-world data on step-up dosing among Chinese breast cancer patients under routine outpatient management, including the early toxicity profile, dose escalation achievement rate at each stage, dose adjustment pathways (prolonged escalation, treatment pause or dose de-escalation), RDI distribution, correlation with quality of life, and baseline factors affecting treatment tolerance and dose target attainment. Therefore, it is necessary to conduct a real-world study focused on Chinese patients to fill the gap in local clinical evidence, and provide a basis for clinical pathway formulation, patient education, and subsequent multicenter validation studies.
研究概览
研究类型
注册 (估计的)
阶段
- 第四阶段
联系人和位置
学习联系方式
- 姓名:Lize Wang, Doctor
- 电话号码:+86-010-88197830
- 邮箱:lize2010@163.com
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Aged ≥18 years;
- Pathologically confirmed breast cancer with ER and/or PR positive, HER2 negative;
- Completed radical mastectomy/radiacal breast surgery;
- Plan to receive abemaciclib combined endocrine therapy for at least 12 weeks, with abemaciclib administered via a step-up dosing regimen;
- ECOG performance status 0-1;
- Adequate organ function meeting medication requirements (routine blood test, liver and renal function, and other indicators consistent with clinical medication safety criteria);
- Signed written informed consent.
Exclusion Criteria:
- Previous exposure to any CDK4/6 inhibitor;
- Active infection or severe infection requiring systemic anti-infective treatment;
- Significant gastrointestinal diseases such as chronic diarrhea, inflammatory bowel disease, short bowel syndrome, which may affect drug absorption or increase the risk of diarrhea;
- Significant baseline hepatic or renal dysfunction, or uncontrolled severe comorbidities judged by the investigator to affect safety or treatment adherence;
- Pregnancy or lactation;
- Any other condition deemed ineligible for enrollment by the investigator.
学习计划
研究是如何设计的?
设计细节
- 主要用途:预防
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的:Dose escalation group
Patients receiving postoperative abemaciclib step-up dosing regimen.
Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).
|
Patients receiving postoperative abemaciclib step-up dosing regimen.
Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).
Patients receiving postoperative abemaciclib step-up dosing regimen.
Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Rate of inadequate dosing
大体时间:From enrollment to the end of treatment at 12 weeks
|
Proportion of patients with inadequate dosing from postoperative treatment initiation to week 12
|
From enrollment to the end of treatment at 12 weeks
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Dose Target Attainment and Treatment Intensity
大体时间:From enrollment to the end of treatment at 12 weeks"
|
Proportion of patients achieving 150 mg BID at Week 12.
|
From enrollment to the end of treatment at 12 weeks"
|
|
QoL deterioration rate
大体时间:From enrollment to the end of treatment at 12 weeks.
|
Proportion of patients experiencing a deterioration in health-related quality of life defined as a decrease of ≥10 points from baseline through EORTC QLQ-C30.
|
From enrollment to the end of treatment at 12 weeks.
|
合作者和调查者
出版物和有用的链接
一般刊物
- Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, Zhang QY, Martinez Rodriguez JL, Campone M, Hamilton E, Sohn J, Guarneri V, Okada M, Boyle F, Neven P, Cortes J, Huober J, Wardley A, Tolaney SM, Cicin I, Smith IC, Frenzel M, Headley D, Wei R, San Antonio B, Hulstijn M, Cox J, O'Shaughnessy J, Rastogi P; monarchE Committee Members and Investigators. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-3998. doi: 10.1200/JCO.20.02514. Epub 2020 Sep 20.
- Mayer EL, Trapani D, Kim SE, Faggen M, Sinclair N, Sanz-Altamira P, Battelli C, Berwick S, Lo S, Acevedo J, Sinclair S, Malcolm A, Varella L, Sammons S, Schumer S, Poorvu PD, Wallace E, Pasternak E, Tayob N, Tolaney SM. TRADE: a phase II trial to assess the tolerability of abemaciclib dose escalation in early-stage HR-positive/HER2-negative breast cancer. Ann Oncol. 2026 Jan;37(1):117-124. doi: 10.1016/j.annonc.2025.09.141. Epub 2025 Oct 17.
- Goetz MP, Cicin I, Testa L, Tolaney SM, Huober J, Guarneri V, Johnston SRD, Martin M, Rastogi P, Harbeck N, Shahir A, Wei R, Andre V, Rugo HS, O'Shaughnessy J. Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study. NPJ Breast Cancer. 2024 Apr 26;10(1):34. doi: 10.1038/s41523-024-00639-1.
- Johnston SRD, Toi M, O'Shaughnessy J, Rastogi P, Campone M, Neven P, Huang CS, Huober J, Jaliffe GG, Cicin I, Tolaney SM, Goetz MP, Rugo HS, Senkus E, Testa L, Del Mastro L, Shimizu C, Wei R, Shahir A, Munoz M, San Antonio B, Andre V, Harbeck N, Martin M; monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023 Jan;24(1):77-90. doi: 10.1016/S1470-2045(22)00694-5. Epub 2022 Dec 6.
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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