Real-World Data of Triplet Combination of Trastuzumab, Lapatinib, and Chemotherapy in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study
Real-World Data of Triplet Combination of Trastuzumab, Lapatinib, and Chemotherapy in HER2-Positive Metastatic Breast Cancer: A Multicenter Retrospective Study
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曲妥珠单抗、拉帕替尼和化疗三联疗法治疗 HER2 阳性转移性乳腺癌的真实世界数据：多中心回顾性研究
DOI：
10.3389/fonc.2020.00271
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发表时间：
2020-03-03
影响因子：
4.7
通讯作者：
Wang, Biyun
中科院分区：
文献类型：
--
作者：
Li, Yi;Gong, Chengcheng;Wang, Biyun
引言：曲妥珠单抗（T）和拉帕替尼（L）联合已被证明可显著改善人表皮生长因子受体2（HER2）阳性且经过大量前期治疗的转移性乳腺癌（MBC）的预后。T和L联合化疗（TLC）是否能进一步提高HER2阳性MBC的疗效仍需进一步研究。本研究的目的是报告TLC在HER2阳性MBC中的首批真实世界数据，包括疗效、安全性和治疗模式。
方法：纳入2013年9月至2019年7月在中国5家机构接受TLC治疗的HER2阳性MBC患者。报告无进展生存期（PFS）、客观缓解率（ORR）、总生存期（OS）、毒性特征和治疗模式。
结果：共纳入285例患者。88.8%的患者之前接触过曲妥珠单抗，49.2%的患者在TLC之前接受过2线或更多线的系统治疗。与T和L联合最常见的化疗方案是卡培他滨（40.7%）和长春瑞滨（21.4%），且几乎1/3的患者在TLC之后接受了维持治疗。中位PFS为10.9个月，而将TLC作为一线治疗的患者中位PFS最长，为20.7个月。之前接受过曲妥珠单抗治疗的患者中位PFS为10.2个月。在之前接受过曲妥珠单抗治疗的患者中，在标准的拉帕替尼加卡培他滨基础上继续使用曲妥珠单抗，中位PFS为11.3个月。T和L联合卡培他滨或长春瑞滨在中位PFS上无显著差异，尽管T和L联合卡培他滨在数值上有延长（11.4个月对8.5个月，P = 0.231）。有脑转移（BM）的患者（考虑颅内和颅外病变）中位PFS也为10.6个月。系统转移治疗的线数是PFS的独立预测因素。中位OS未达到。277例患者纳入ORR分析。ORR为42.6%。三联组合的毒性是可耐受的，最常见的3级和4级不良事件是中性粒细胞减少（16.8%）。
结论：TLC在HER2阳性MBC中显示出有前景的疗效和可耐受的安全性，即使在有脑转移的患者中也是如此，为临床实践提供了理论基础。
Introduction: Combination of trastuzumab (T) and lapatinib (L) has been showed to significantly improve the prognosis of HER2+ heavily pretreated metastatic breast cancer (MBC). Whether TL combined chemotherapy (TLC) can further improve the efficacy in HER2+ MBC remains to be further studied. The aim of the study was to report the first real-world data of TLC in HER2+ MBC, including the efficacy, safety and treatment patterns.Methods: Patients with HER2+ MBC treated with TLC in 5 institutions of China from September 2013 to July 2019 were included. Progression free survival (PFS), objective response rate (ORR), overall survival (OS), toxicity profile and treatment pattern were reported.Results: A total of 285 patients were included. 88.8% were exposed to trastuzumab and 49.2% received 2 or more lines of systematic therapy before TLC previously. The most common chemotherapy regimens combined with TL were capecitabine (40.7%) and vinorelbine (21.4%) and almost 1/3 received maintenance treatment after TLC. Median PFS was 10.9 months while patients received TLC as first line treatment showed longest median PFS of 20.7 months. Patients pretreated with trastuzumab showed a median PFS of 10.2 months. In patients who pretreated with trastuzumab, the continuation of trastuzumab on the basis of standard lapatinib plus capecitabine had a median PFS of 11.3 months. TL combined with capecitabine or vinorelbine showed no significant difference in median PFS, though TL combined with capecitabine had numerically prolongation (11.4 vs. 8.5 months, p = 0.231). Patients had brain metastasis (BM) also showed a median PFS (intracranial and extracranial lesions considered) of 10.6 months. Lines of systematic metastatic treatment was an independent predictive factor of PFS. The median OS was not reached. Two hundred and seventy seven patients were included in ORR analysis. ORR was 42.6%. Toxicities of triplet combinations were tolerable and the most common grade 3 and 4 adverse events were neutropenia (16.8%).Conclusions: TLC demonstrated promising effects and tolerable safety in HER2+MBC, even in patients with BM, providing a theoretical basis for clinical practice.