Purpose: Despite accumulating evidence on dual blockade of HER2 for locally advanced HER2-positive breast cancer, no robust evidence supports the addition of pyrotinib to trastuzumab in the neoadjuvant setting. The NeoATP trial aimed to evaluate the efficacy and safety of pyrotinib with neoadjuvant trastuzumab and chemotherapy. Patients and Methods: The phase II NeoATP trial included female patients with histologically confirmed stage IIA to IIIC and HER2-positive primary invasive breast cancer. Eligible patients received pyrotinib and trastuzumab with weekly paclitaxel–cisplatin neoadjuvant chemotherapy for four cycles. The primary endpoint was pathologic complete response (pCR; ypT0 ypN0) rate. Key secondary endpoints included locoregional pCR (ypT0/is ypN0) rate, biomarker analysis, and safety. Results: Among 53 enrolled patients (median age, 47 years; 73.58% stage III), 52 completed the study treatment and surgery. Overall, 37 patients (69.81%) achieved pCR. For women with hormone receptor–negative and –positive tumors, the pCR rates were 85.71% and 59.38% (P = 0.041), while the corresponding rates were 69.23% and 70.00%, respectively, for those with and without PIK3CA mutation (P = 0.958). The most frequently reported Grade 3 to 4 adverse events were diarrhea (45.28%), leukopenia (39.62%), and neutropenia (32.08%). No deaths occurred, and no left ventricular ejection fraction <50% or >10 points drop from baseline to before surgery was reported. Conclusions: The addition of pyrotinib to trastuzumab plus chemotherapy is an efficacious and safe regimen for patients with HER2-positive locally advanced breast cancer in the neoadjuvant setting. The randomized controlled clinical trial is warranted to validate our results.

中文翻译：

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新辅助曲妥珠单抗和吡咯替尼治疗局部晚期 HER2 阳性乳腺癌 (NeoATP)：II 期研究的初步分析

目的：尽管越来越多的证据表明双重阻断 HER2 治疗局部晚期 HER2 阳性乳腺癌，但没有强有力的证据支持在新辅助治疗中在曲妥珠单抗中添加吡咯替尼。NeoATP 试验旨在评估吡咯替尼联合新辅助曲妥珠单抗和化疗的疗效和安全性。患者和方法：II 期 NeoATP 试验纳入了经组织学证实为 IIA 至 IIIC 期且 HER2 阳性原发性浸润性乳腺癌的女性患者。符合条件的患者接受吡咯替尼和曲妥珠单抗治疗，每周接受紫杉醇-顺铂新辅助化疗，为期四个周期。主要终点是病理完全缓解（pCR；ypT0 ypN0）率。主要次要终点包括局部 pCR (ypT0/is ypN0) 率、生物标志物分析和安全性。结果：在 53 名入组患者中（中位年龄，47岁；73.58% III期），52人完成了研究治疗和手术。总体而言，37 名患者 (69.81%) 达到了 pCR。对于激素受体阴性和阳性肿瘤的女性，pCR 率分别为 85.71% 和 59.38% (P = 0.041)，而对于有和没有 PIK3CA 突变的女性，相应的比率分别为 69.23% 和 70.00% (P = 0.958）。最常报告的 3 至 4 级不良事件是腹泻（45.28%）、白细胞减少（39.62%）和中性粒细胞减少（32.08%）。没有发生死亡，并且没有报告左心室射血分数从基线到手术前下降＜50％或＞10个点。结论：在曲妥珠单抗联合化疗中添加吡咯替尼对于新辅助治疗的 HER2 阳性局部晚期乳腺癌患者来说是一种有效且安全的治疗方案。