Impact of low HER2 expression on response to CDK4/6 inhibitor treatment in advanced HR + /HER2- breast cancer: a multicenter real-world data analysis.

IF 2.1 3区医学 Q2 OBSTETRICS & GYNECOLOGY

Archives of Gynecology and Obstetrics Pub Date : 2024-10-07 DOI:10.1007/s00404-024-07761-2

Damian J Ralser, Verena Kiver, Erich-Franz Solomayer, Caroline Neeb, Jens-Uwe Blohmer, Alina V Abramian, Nicolai Maass, Florian Schütz, Cornelia Kolberg-Liedtke, Carolin Müller, Anna-Christina Rambow

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引用次数: 0

Abstract

Purpose: CDK4/6 inhibitors (CDK4/6i) represent the first-line therapy approach of choice for patients with hormone receptor-positive, HER2-negative advanced breast cancer (HR + /HER-ABC). Approximately 50% of HR + /HER2-ABC displays low HER2 expression (HER2 low). Recent data emerging from the DESTINY-Breast04 trial demonstrated practice-changing efficacy of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in patients with low HER2 expression. Here, we aimed to analyze the impact of low HER2 expression on CDK4/6i therapy response in a well-characterized multicenter HR + /HER-ABC cohort.

Methods: Patients diagnosed with HR + /HER2-ABC who were treated with CDK4/6i in clinical routine between November 2016 and December 2020 at four certified German Breast Cancer Centers were retrospectively identified. The cohort was stratified according to graduation of positivity in HER2 immunohistochemistry (IHC; HER2 zero = IHC score 0 and HER2 low = IHC score 1 + , 2 + /fluorescence in situ hybridization negative). Subgroups were analyzed with regard to progression-free survival (PFS) following CDK4/6i initiation.

Findings: The study cohort comprised n = 448 patients. For n = 311 patients, HER2 status from the metastatic site was available. n = 91 (29.3%) cases were HER2 zero and n = 220 cases (70.7%) were HER2 low. There was no significant difference in PFS between the two groups (PFS: 17 months versus 18 months, log-rank p = 0.42). Further, we examined the influence of HER2 expression changes between primary and metastatic tissue (n = 171; HER2 gain/HER2 loss/HER2 stable expression) on CDK4/6i treatment response. Again, there was no significant difference between these three groups, respectively (PFS: 16 months versus 13 months versus 17 months, log-rank p = 0.86).

Conclusions: In our analysis, HER2 status did not have a significant impact on treatment response to CDK4/6i.

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HER2低表达对晚期HR + /HER2-乳腺癌CDK4/6抑制剂治疗反应的影响：多中心真实世界数据分析。

目的：CDK4/6 抑制剂（CDK4/6i）是激素受体阳性、HER2 阴性晚期乳腺癌（HR + /HER-ABC）患者的首选一线治疗方法。约 50% 的 HR + /HER2-ABC 患者 HER2 表达较低（HER2 低）。DESTINY-Breast04试验的最新数据显示，抗体药物共轭物曲妥珠单抗德鲁司坦（T-DXd）对HER2低表达患者具有改变临床实践的疗效。在此，我们旨在分析低HER2表达对CDK4/6i治疗反应的影响：回顾性鉴定2016年11月至2020年12月期间在德国四家认证乳腺癌中心接受CDK4/6i临床常规治疗的HR + /HER2-ABC患者。根据 HER2 免疫组化（IHC；HER2 零 = IHC 得分为 0，HER2 低 = IHC 得分为 1 +、2 + /荧光原位杂交阴性）阳性率的分级对组群进行分层。研究人员根据CDK4/6i启动后的无进展生存期（PFS）对亚组进行了分析：研究队列由 n = 448 名患者组成。91例（29.3%）HER2为零，220例（70.7%）HER2为低。两组患者的 PFS 无明显差异（PFS：17 个月对 18 个月，log-rank p = 0.42）。此外，我们还研究了原发组织和转移组织（n = 171；HER2 增高/HER2 降低/HER2 稳定表达）的 HER2 表达变化对 CDK4/6i 治疗反应的影响。同样，这三组之间分别没有明显差异（PFS：16个月对13个月对17个月，log-rank p = 0.86）：在我们的分析中，HER2状态对CDK4/6i的治疗反应没有显著影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of Gynecology and Obstetrics 医学-妇产科学

CiteScore

4.70

自引率

15.40%

发文量

493

审稿时长

1 months

期刊介绍： Founded in 1870 as "Archiv für Gynaekologie", Archives of Gynecology and Obstetrics has a long and outstanding tradition. Since 1922 the journal has been the Organ of the Deutsche Gesellschaft für Gynäkologie und Geburtshilfe. "The Archives of Gynecology and Obstetrics" is circulated in over 40 countries world wide and is indexed in "PubMed/Medline" and "Science Citation Index Expanded/Journal Citation Report". The journal publishes invited and submitted reviews; peer-reviewed original articles about clinical topics and basic research as well as news and views and guidelines and position statements from all sub-specialties in gynecology and obstetrics.