晚期乳腺癌靶向治疗失败后老选手

　　2007年，拉帕替尼被批准联合卡培他滨用于曲妥珠单抗治疗失败的HER2阳性转移性乳腺癌患者。不过，对于既往帕妥珠单抗标准一线治疗和曲妥珠单抗-恩特星（T-DM1）标准二线治疗失败的患者，拉帕替尼缺乏疗效数据。

　　2019年4月11日，施普林格·自然《乳腺癌研究与治疗》在线发表美国德克萨斯大学MD安德森癌症中心的研究报告，评定了拉帕替尼对于既往接受过帕妥珠单抗和（或）T-DM1的HER2阳性转移性乳腺癌患者人群的疗效。

　　该队列研究对2003～2017年在MD安德森癌症中心接受拉帕替尼的520例HER2阳性转移性乳腺癌患者进行回顾分析，将其中43例接受过帕妥珠单抗或T-DM1作为目标组、其余477例作为对照组，对结局指标进行评估，包括临床获益率、最佳缓解率、拉帕替尼持续用药时间、进展时间，通过生存曲线法进行生存分析

　　结果，目标组、对照组相比，临床获益率分别为28%、40%（95%置信区间：10～32、36～45），拉帕替尼持续用药时间分别为中位5个月、6.7个月（95%置信区间：3.0～9.0、5.9～8.0）。两组的初发转移、复发转移患者相比，中位进展时间和总生存时间较长。

　　因此，该研究结果表明，对于既往曲妥珠单抗、帕妥珠单抗和（或）T-DM1失败后的HER2阳性转移性乳腺癌，拉帕替尼仍然是有效、可行的治疗选择之一。

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Breast Cancer Res Treat. 2019 Apr 11.

Lapatinib activity in metastatic human epidermal growth factor receptor 2-positive breast cancers that received prior therapy with trastuzumab, pertuzumab, and/or ado-trastuzumab emtansine (T-DM1).

Baez-Vallecillo L, Raghavendra AS, Hess KR, Barcenas CH, Moulder SL, Tripathy D, Valero V, Murthy RK.

The University of Texas MD Anderson Cancer Center, Houston, USA.

PURPOSE: Lapatinib (L) is approved in combination with capecitabine or letrozole for patients with trastuzumab-resistant HER2-positive metastatic breast cancer (MBC). However, there is no efficacy data of L in patients who received prior pertuzumab (P) and ado-trastuzumab emtansine (T-DM1), now included as standard first- and second-line therapies, respectively. The goal of this study was to assess the efficacy of L in a contemporary patient population that received prior P and/or T-DM1.

METHODS: We identified patients with HER2-positive MBC who received L (n=520) between 2003 and 2017 at MD Anderson Cancer Center and selected a target cohort who received L after prior P or T-DM1 (n=43) with the remaining included in the comparison cohort (n=477). We evaluated outcome measures including clinical benefit rate (CBR), best tumor response (BTR), duration on L, and time to progression (TTP). Survival analyses used Kaplan-Meier statistics.

RESULTS: CBR was 28% (95% CI 10-32) for the target cohort and 40% (95% CI 36-45) for the comparison cohort. The median duration on L was 5 months (95% CI 3.0-9.0) in the target cohort and 6.7 months (5.9-8.0) in the comparison cohort. In both cohorts, the median time to progression (TTP) and overall survival (OS) were longer in patients with de novo metastatic disease compared to patients with disease recurrence.

CONCLUSION: L-based therapy is an active therapeutic option and remains a viable option for HER2+MBC after prior trastuzumab, P and/or T-DM1.

KEYWORDS: Lapatinib Trastuzumab Pertuzumab T-DM1 HER2 Breast cancer Metastatic

PMID: 30977027

DOI: 10.1007/s10549-018-05081-z