背景:HER2阳性,雌激素受体阳性乳腺癌(HER2+,ER+BC)是一种独特的疾病亚型,与HER2+相比,对化疗加HER2靶向治疗的反应较差,ER阴性BC。双向串扰导致HER2和ER途径的合作,这可能会驱动治疗阻力;因此,同时联合靶向可以优化HER2+患者的治疗效果和生存结果,ER+BC。HER2+转移性BC(mBC)患者的一线(1L)治疗是帕妥珠单抗,曲妥珠单抗,紫杉烷化疗.在临床实践中,双重HER2阻断加上固定数量的化疗周期作为诱导治疗,以最大化肿瘤反应,随后给予HER2靶向维持治疗作为长期疾病控制的更耐受方案。对于肿瘤共表达ER的患者,可以增加维持内分泌治疗(ET),但由于缺乏来自随机临床试验的数据,研究维持ET+双重HER2阻断与单独使用双重HER2阻断相比的优越性,因此摄取量存在差异.Giredestrant,一种新型口服选择性ER拮抗剂和降解剂,在ER+患者的I-II期试验中显示出有希望的临床活性和可管理的安全性,HER2阴性BC,在HER2共表达的患者中具有治疗潜力。
方法:第三阶段,随机化,开放标签,双臂研究旨在招募812名HER2+患者,ER+局部晚期(LA)/mBC进入诱导期(帕妥珠单抗和曲妥珠单抗的固定剂量组合用于皮下注射[PHFDCSC]加紫杉烷),使730名患者1:1随机分配至维持期(giredestrant加PHFDCSC或PHFDCSC[加可选ET]),按疾病部位分层(内脏与非内脏),LA/转移性表现的类型(从头与复发),对诱导治疗的最佳总体反应(部分/完全反应与稳定疾病),并打算给ET(是与否)。主要终点是研究者评估的无进展生存期。次要终点包括总生存期,客观反应率,临床获益率,响应的持续时间,安全,和患者报告的结果。
结论:heredERABC将讨论giredeststrant加双重HER2阻断是否优于单独的双重HER2阻断,为了告知在临床实践中使用该组合来维持HER2患者的1L治疗,ER+LA/mBC。
背景:ClinicalTrials.gov,NCT05296798;2022年3月25日注册。协议3.0版(2022年11月18日)。
背景:F霍夫曼-拉罗氏有限公司,Grenzacherstrasse1244070,巴塞尔,瑞士。
BACKGROUND: HER2-positive, estrogen receptor-positive breast cancer (HER2+, ER+ BC) is a distinct disease subtype associated with inferior response to chemotherapy plus HER2-targeted therapy compared with HER2+, ER-negative BC. Bi-directional crosstalk leads to cooperation of the HER2 and ER pathways that may drive treatment resistance; thus, simultaneous co-targeting may optimize treatment impact and survival outcomes in patients with HER2+, ER+ BC. First-line (1L) treatment for patients with HER2+ metastatic BC (mBC) is
pertuzumab, trastuzumab, and taxane chemotherapy. In clinical practice, dual HER2 blockade plus a fixed number of chemotherapy cycles are given as induction therapy to maximize tumor response, with subsequent HER2-targeted maintenance treatment given as a more tolerable regimen for long-term disease control. For patients whose tumors co-express ER, maintenance endocrine therapy (ET) can be added, but uptake varies due to lack of data from randomized clinical trials investigating the superiority of maintenance ET plus dual HER2 blockade versus dual HER2 blockade alone. Giredestrant, a novel oral selective ER antagonist and degrader, shows promising clinical activity and manageable safety across phase I-II trials of patients with ER+, HER2-negative BC, with therapeutic potential in those with HER2 co-expression.
METHODS: This phase III, randomized, open-label, two-arm study aims to recruit 812 patients with HER2+, ER+ locally advanced (LA)/mBC into the induction phase (fixed-dose combination of
pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] plus a taxane) to enable 730 patients to be randomized 1:1 to the maintenance phase (giredestrant plus PH FDC SC or PH FDC SC [plus optional ET]), stratified by disease site (visceral versus non-visceral), type of LA/metastatic presentation (de novo versus recurrent), best overall response to induction therapy (partial/complete response versus stable disease), and intent to give ET (yes versus no). The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include overall survival, objective response rate, clinical benefit rate, duration of response, safety, and patient-reported outcomes.
CONCLUSIONS: heredERA BC will address whether giredestrant plus dual HER2 blockade is superior to dual HER2 blockade alone, to inform the use of this combination in clinical practice for maintenance 1L treatment of patients with HER2+, ER+ LA/mBC.
BACKGROUND: ClinicalTrials.gov, NCT05296798; registered on March 25, 2022. Protocol version 3.0 (November 18, 2022).
BACKGROUND: F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124 4070, Basel, Switzerland.