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.

patients_and_methods

This open-label, randomized, phase II study enrolled patients aged ≥18 years with stage II-III HER2-positive breast cancer.

这项开放标签、随机、II期研究招募了年龄≥18岁的II-III期HER2阳性乳腺癌患者。

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.

患者被随机分配（1:1:1）接受新辅助治疗，分别使用SHR-A1811单药治疗、SHR-A1811联合吡咯替尼治疗，或紫杉醇白蛋白结合型联合卡铂、曲妥珠单抗和帕妥珠单抗（PCbHP）治疗24周。

The primary endpoint was pathological complete response (pCR).

主要终点是病理完全缓解（pCR）。

Safety was analysed in patients who received at least one dose of study medication.

分析了至少接受一剂研究药物患者的药物安全性。

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).

在2022年12月27日至2024年2月11日期间，265名患者被随机分配到新辅助治疗组，其中单药SHR-A1811组（n=87），SHR-A1811联合吡咯替尼组（n=88），或PCbHP组（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.

基线特征均衡；约45%的患者为激素受体（HR）阳性，70%的患者为III期。

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.

单药SHR-A1811的pCR率为63.2%（HR阳性为50%，HR阴性为74.5%），SHR-A1811联合吡罗替尼的pCR率为62.5%（HR阳性为44.7%，HR阴性为76%），PCbHP的pCR率为64.4%（HR阳性为54.1%，HR阴性为71.7%），各组之间无显著差异。

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.

在使用单药SHR-A1811的患者中，有44.8%发生了3级或更高级别的治疗相关不良事件，在SHR-A1811联合吡咯替尼治疗的患者中这一比例为71.6%，而在PCbHP治疗的患者中为38.8%。

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.

在SHR-A1811治疗的患者中，有1名患者经历了2级间质性肺病，在SHR-A1811联合吡咯替尼治疗的患者中，有9.1%的患者经历了3级腹泻，但没有治疗相关的死亡发生。

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.

这是首个报告第三代HER2靶向抗体药物偶联物(ADC)在HER2阳性乳腺癌新辅助治疗中疗效和安全性的研究。

SHR-A1811 showed robust activity, with a tolerable safety profile.

SHR-A1811显示出强大的活性，并具有可接受的安全性特征。