新辅助SHR-A1811联合或不联合吡咯替尼治疗局部晚期或早期HER2阳性乳腺癌女性的疗效和安全性：一项随机、开放标签的II期试验
Efficacy and safety of neoadjuvant SHR-A1811 with or without pyrotinib in women with locally advanced or early HER2-positive breast cancer: a randomized, open-label, phase II trial.
作者信息
Li J J, Wang Z H, Chen L, Zhang W J, Ma L X X, Wu J, Liu G Y, Hou Y F, Yu K D, Di G H, Fan L, Jiang Y Z, Jiang S H, Liang Q N, Shen Y, Shao Z-M
机构信息
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
出版信息
Ann Oncol. 2025 Jun;36(6):651-659. doi: 10.1016/j.annonc.2025.02.011. Epub 2025 Mar 4.
BACKGROUND
Standard neoadjuvant regimens for human epidermal growth factor receptor 2 (HER2)-positive breast cancer include trastuzumab and pertuzumab combined with chemotherapy, and the efficacy and safety of third-generation HER2-directed antibody-drug conjugate (ADC) remain to be elucidated.
PATIENTS AND METHODS
This open-label, randomized, phase II study enrolled patients aged ≥18 years with stage II-III HER2-positive breast cancer. Patients were randomly assigned (1 : 1 : 1) to receive neoadjuvant treatment either with SHR-A1811 monotherapy, SHR-A1811 with pyrotinib, or nab-paclitaxel combined with carboplatin, trastuzumab, and pertuzumab (PCbHP) for 24 weeks. The primary endpoint was pathological complete response (pCR). Safety was analysed in patients who received at least one dose of study medication.
RESULTS
Between 27 December 2022 and 11 February 2024, 265 patients were randomly allocated to neoadjuvant, mono-SHR-A1811 (n = 87), SHR-A1811 plus pyrotinib (n = 88), or PCbHP (n = 90). The baseline characteristics were well balanced; ∼45% of the patients were hormone receptor (HR) positive, and 70% of the patients were stage III. The pCR rate was 63.2% for mono-SHR-A1811 (50% for HR positive and 74.5% for HR negative), 62.5% for SHR-A1811 plus pyrotinib (44.7% for HR positive and 76% for HR negative), and 64.4% for PCbHP (54.1% for HR positive and 71.7% for HR negative), with no significant difference between the groups. Grade ≥3 treatment-related adverse events occurred in 44.8% of patients with mono-SHR-A1811, 71.6% with SHR-A1811 plus pyrotinib, and 38.8% with PCbHP. One patient experienced grade 2 interstitial lung disease in SHR-A1811, 9.1% of patients experienced grade 3 diarrhoea in SHR-A1811 plus pyrotinib, and no treatment-related deaths occurred.
CONCLUSIONS
This is the first study to report the efficacy and safety of third-generation HER2-directed ADC in the neoadjuvant setting for HER2-positive breast cancer. SHR-A1811 showed robust activity, with a tolerable safety profile.
背景
人表皮生长因子受体2（HER2）阳性乳腺癌的标准新辅助治疗方案包括曲妥珠单抗和帕妥珠单抗联合化疗，而第三代HER2导向抗体药物偶联物（ADC）的疗效和安全性仍有待阐明。
患者与方法
这项开放标签、随机、II期研究纳入了年龄≥18岁的II-III期HER2阳性乳腺癌患者。患者被随机分配（1:1:1）接受新辅助治疗，分别为SHR-A1811单药治疗、SHR-A1811联合吡咯替尼，或白蛋白结合型紫杉醇联合卡铂、曲妥珠单抗和帕妥珠单抗（PCbHP），疗程为24周。主要终点为病理完全缓解（pCR）。对接受至少一剂研究药物的患者进行安全性分析。
结果
在2022年12月27日至2024年2月11日期间，265例患者被随机分配接受新辅助治疗，其中SHR-A1811单药治疗组（n = 87）、SHR-A1811联合吡咯替尼组（n = 88）或PCbHP组（n = 90）。基线特征均衡良好；约45%的患者为激素受体（HR）阳性，70%的患者为III期。SHR-A1811单药治疗组的pCR率为63.2%（HR阳性患者为50%，HR阴性患者为74.5%），SHR-A1811联合吡咯替尼组为62.5%（HR阳性患者为44.7%，HR阴性患者为76%），PCbHP组为64.4%（HR阳性患者为54.1%，HR阴性患者为71.7%），各组之间无显著差异。SHR-A1811单药治疗组44.8%的患者发生≥3级治疗相关不良事件，SHR-A1811联合吡咯替尼组为71.6%，PCbHP组为38.8%。SHR-A1811组有1例患者发生2级间质性肺病，SHR-A1811联合吡咯替尼组9.1%的患者发生3级腹泻，未发生与治疗相关的死亡。
结论
这是第一项报告第三代HER2导向ADC在HER2阳性乳腺癌新辅助治疗中的疗效和安全性的研究。SHR-A1811显示出强大的活性，安全性可耐受。
Zotero 插件