目的：为了探索吡咯替尼联合卡培他滨节拍化疗在人表皮生长因子2（Human epidermal growth factor receptor 2, HER2）阳性晚期乳腺癌（metastatic breast cancer, MBC）患者中的疗效与安全性，我们进行了一项前瞻性II期单臂研究。

方法：给予HER2阳性晚期乳腺癌患者口服吡咯替尼与卡培他滨，吡咯替尼的给药剂量为每日一次，每次400mg；卡培他滨以节拍化疗的方式给药，剂量为每日三次，每次500mg。研究的主要终点是无进展生存期。其他终点包括客观缓解率、总生存期、疾病控制率和安全性。

结果：该研究一共纳入50例HER2阳性晚期乳腺癌患者，其中1例因用药过程中未规律用药被剔除出研究。在纳入最终分析的49例患者中，中位无进展生存期（median progression-free survival, mPFS）为14.5个月（95%CI 11.2-29），总生存（overall survival, OS）分别28.4个月（95%CI 21.7-NA）。客观缓解率（objective response rate, ORR）和疾病控制率（disease control rate, DCR）分别为34.7%和81.6%，其中2例患者达到完全缓解（complete response, CR）（4.1%），15例患者出现部分缓解（partial response, PR）（30.6%），23例患者在治疗过程中维持疾病稳定（stable disease, SD）（46.9%）。晚期一线或二线治疗的mPFS为14.9个月，生存获益显著高于晚期二线以后11.6个月的mPFS。最常见的治疗相关不良事件（adverse events, AE）包括手足综合征、腹泻、呕吐和恶心。3级不良事件发生在11例患者中，包括手足综合症（12.2%），腹泻（12.2%），呕吐（4.1%），食欲下降（4.1%）和恶心（2.0%）。在治疗过程中一共有2例患者出现4级不良事件，均为腹泻（4.0%）。

结论：吡咯替尼联合卡培他滨节拍化疗在HER2阳性晚期乳腺癌患者中具有较好的疗效和良好的耐受性，是一项具有前景的治疗方案。

Purpose: To analyze the safety and efficacy of orally administered metronomic capecitabine plus pyrotinib in HER2-positive metastatic breast cancer (MBC) patients, we conducted a prospective phase II study with a single-arm design.

Methods: HER2-positive patients received oral metronomic capecitabine 500 mg three times a day and pyrotinib 400 mg per day. The primary endpoint focused on progression-free survival (PFS). Other endpoints encompassed objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR) and safety.

Results: This study included a total of 50 patients with HER2-positive advanced breast cancer, with one patient excluded from the study due to irregular medication during the treatment process. Among the 49 patients included in the final analysis, the median progression-free survival (mPFS) and overall survival (OS) were 14.5 months (95% CI 11.2-29) and 28.4 months (95% CI 21.7-NA), respectively. The objective response rate (ORR) was 34.7%, and the disease control rate (DCR) was 81.6%, including 2 cases of complete response (CR) (4.1%), 15 cases of partial response (PR) (30.6%), and 23 cases of stable disease (SD) (46.9%). The mPFS for first- or second-line treatment was 14.9 months, demonstrating a significantly higher survival benefit compared to the mPFS of 11.6 months in advanced stages beyond the second line of treatment. The most frequent treatment-related adverse events (AEs) encompassed hand-foot syndrome, diarrhea, vomiting, and nausea. Grade 3 AEs occurred in 11 patients, including hand-foot syndrome (12.2%), diarrhea (12.2%), vomiting (4.1%), decreased appetite (4.1%), and nausea (2.0%). 2 grade 4 adverse events of diarrhea (4.0%) was observed.

Conclusion: The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2-positive advanced breast cancer patients.