完成腋窝淋巴结清扫以确定 pN2-3 状态作为 CDK4/6 抑制剂辅助治疗的适应症:SENOMAC 随机三期试验的事后分析。

IF 41.6 1区 医学 Q1 ONCOLOGY
Lancet Oncology Pub Date : 2024-09-01 Epub Date: 2024-08-06 DOI:10.1016/S1470-2045(24)00350-4
Jana de Boniface, Matilda Appelgren, Robert Szulkin, Sara Alkner, Yvette Andersson, Leif Bergkvist, Jan Frisell, Oreste Davide Gentilini, Michalis Kontos, Thorsten Kühn, Dan Lundstedt, Birgitte Vrou Offersen, Roger Olofsson Bagge, Toralf Reimer, Malin Sund, Peer Christiansen, Lisa Rydén, Tove Filtenborg Tvedskov
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引用次数: 0

摘要

背景:对于腔隙性乳腺癌,辅助CDK4/6抑制剂(如阿培莫司利)可提高无浸润生存率。对于T1-2、1-2级肿瘤和1或2个前哨淋巴结转移的患者,完成腋窝淋巴结清扫(cALND)是目前唯一能发现4个或更多结节转移(pN2-3)的预后工具,这也是在这种情况下辅助阿巴西利布的唯一适应症。然而,这项技术可能会导致患者的手臂发病率大幅上升。我们的目的是在正在进行的 SENOMAC 试验中,从患者个体层面务实地描述这一策略的潜在益处和害处:在 SENOMAC 随机三期试验中,来自五个欧洲国家(丹麦、德国、希腊、意大利和瑞典)67 个地点的临床结节阴性 T1-T3 乳腺癌且有一个或两个前哨淋巴结大转移的 18 岁或以上任何表现状态的患者通过按国家分层的包块随机化(随机包块大小为 2 和 4)被随机分配(1:1)到 cALND 或省略 cALND(即只进行前哨淋巴结活检)。主要结果是总生存期,尚未报告。在这项事后分析中,从SENOMAC按方案人群中挑选出了管腔雌激素受体阳性、HER2阴性、T1-2、组织学分级1-2级、肿瘤大小为5厘米或更小的乳腺癌患者,以符合monarchE试验队列1的特征,这些患者只有在发现有4个或更多结节转移时才有阿贝单抗辅助治疗的指征。主要研究目标是利用 monarchE 试验队列 1 中的侵袭性无疾病生存事件数据,确定 cALND 术后 1 年出现患者报告的严重或非常严重的手臂肢体功能障碍(以淋巴水肿功能、残疾和健康 [Lymph-ICF] 问卷测量)的患者人数,以避免在 5 年时发生一次侵袭性无疾病生存事件,并辅助阿贝昔单抗治疗 2 年。SENOMAC试验已在ClincialTrials.gov上注册,编号为NCT02240472,目前已结束注册,正在进行中:2015年1月31日至2021年12月31日期间,2766名患者加入SENOMAC,并被随机分配至cALND(1384人)或仅前哨节点活检(1382人),其中2540人被纳入按方案人群。2540名患者中有1705人(67%)符合这项事后研究的资格标准,其中802人(47%)进行了cALND,903人(53%)仅进行了前哨淋巴结活检。随机化时的中位年龄为 62 岁(IQR 52-71),1705 例患者中有 1699 例(>99%)为女性,6 例(2 例检验 p解释:作为一种可能确定阿巴西利适应症的方法,以及随后通过2年的阿巴西利辅助治疗避免5年无病生存事件的方法,cALND具有严重或非常严重的手臂发病率的巨大风险,因此不应鼓励为此目的进行cALND:瑞典研究理事会、瑞典癌症协会、北欧癌症联盟和瑞典乳腺癌协会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Completion axillary lymph node dissection for the identification of pN2-3 status as an indication for adjuvant CDK4/6 inhibitor treatment: a post-hoc analysis of the randomised, phase 3 SENOMAC trial.

Background: In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1-2, grade 1-2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2-3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial.

Methods: In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1-T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1-2, histological grade 1-2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing.

Findings: Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52-71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6-59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery.

Interpretation: As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose.

Funding: Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.

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来源期刊
Lancet Oncology
Lancet Oncology 医学-肿瘤学
CiteScore
62.10
自引率
1.00%
发文量
913
审稿时长
3-8 weeks
期刊介绍: The Lancet Oncology is a trusted international journal that addresses various topics in clinical practice, health policy, and global oncology. It covers a wide range of cancer types, including breast, endocrine system, gastrointestinal, genitourinary, gynaecological, haematological, head and neck, neurooncology, paediatric, thoracic, sarcoma, and skin cancers. Additionally, it includes articles on epidemiology, cancer prevention and control, supportive care, imaging, and health-care systems. The journal has an Impact Factor of 51.1, making it the leading clinical oncology research journal worldwide. It publishes different types of articles, such as Articles, Reviews, Policy Reviews, Personal Views, Clinical Pictures, Comments, Correspondence, News, and Perspectives. The Lancet Oncology also collaborates with societies, governments, NGOs, and academic centers to publish Series and Commissions that aim to drive positive changes in clinical practice and health policy in areas of global oncology that require attention.
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