Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
BMC Cancer. 2024 Oct 18;24(1):1290. doi: 10.1186/s12885-024-13041-8.
Exploration of novel combination mode of pyrotinib and chemotherapy for heavily pretreated HER2-positive metastatic breast cancer (MBC) and how to balance survival benefits and compliance are still urgent problems in clinical practice. The current single-arm prospective phase II study aimed to evaluate the efficacy and safety of pyrotinib in combination with metronomic oral etoposide in heavily pretreated HER2-positive MBC.
HER2-positive MBC patients previously treated with trastuzumab were enrolled to receive oral pyrotinib 400 mg per day and metronomic oral etoposide 50 mg per day d1-21 every 28 days, until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), and safety.
22 patients were enrolled with a median of 4 prior treatment regimens for MBC. During the follow-up of 20 evaluable patients, the median PFS was 9.0 months (95% CI, 7.6-10.4 months), and the median OS was 27.0 months (95%CI, 20.9-33.1 months). The ORR was 30% (6/20), the DCR was 80% (16/20), and the CBR was 65% (13/20). The most common grade 3 adverse events (AEs) included nausea (15%), vomiting (15%), diarrhea (5%), anemia (5%), and peripheral neuropathy (5%). No grade 4 or lethal AEs were observed.
The combination of pyrotinib with metronomic oral etoposide has achieved promising clinical benefits in heavily pretreated HER2-positive MBC, with acceptable and manageable toxicity.
Registry number: NCT03923179. Registered April 18, 2019.
探索吡咯替尼联合化疗治疗曲妥珠单抗治疗后复发的人表皮生长因子受体 2（HER2）阳性转移性乳腺癌（MBC）的新联合模式，以及如何平衡生存获益和患者依从性，仍然是临床实践中的迫切问题。本项单臂前瞻性 II 期研究旨在评估吡咯替尼联合低剂量口服依托泊苷在曲妥珠单抗治疗后复发的 HER2 阳性 MBC 患者中的疗效和安全性。
纳入既往接受过曲妥珠单抗治疗的 HER2 阳性 MBC 患者，接受吡咯替尼 400mg/天和低剂量口服依托泊苷 50mg/天（d1-21），每 28 天为一个周期，直至疾病进展或出现不可接受的毒性。主要终点为无进展生存期（PFS）。次要终点为客观缓解率（ORR）、疾病控制率（DCR）、临床获益率（CBR）、总生存期（OS）和安全性。
共入组 22 例患者，中位既往治疗方案数为 4 种。在 20 例可评估患者的随访中，中位 PFS 为 9.0 个月（95%CI，7.6-10.4 个月），中位 OS 为 27.0 个月（95%CI，20.9-33.1 个月）。ORR 为 30%（6/20），DCR 为 80%（16/20），CBR 为 65%（13/20）。最常见的 3 级不良事件（AE）包括恶心（15%）、呕吐（15%）、腹泻（5%）、贫血（5%）和周围神经病变（5%）。未观察到 4 级或致命 AE。
吡咯替尼联合低剂量口服依托泊苷在曲妥珠单抗治疗后复发的 HER2 阳性 MBC 患者中取得了有前景的临床获益，且毒性可耐受且易于管理。
注册号：NCT03923179。注册日期：2019 年 4 月 18 日。
