对于HER2阳性晚期乳腺癌，如果曲妥珠单抗、拉帕替尼治疗失败，可以选择抗体缀合化疗药物恩美曲妥珠单抗（T-DM1）或中国原创HER1、HER2、HER4酪氨酸激酶不可逆抑制剂药物吡咯替尼。不过，吡咯替尼与T-DM1之间，目前缺乏头对头的随机对照研究。
2021年1月，转化医学会旗下《转化医学年鉴》正式发表解放军总医院第五医学中心李峰、许凤锐、李健斌、王涛、边莉、张少华、江泽飞等学者的真实世界研究报告，首次比较了吡咯替尼或T-DM1对于中国HER2阳性晚期乳腺癌曲妥珠单抗、拉帕替尼治疗失败患者的有效性和安全性。
该单中心小样本回顾研究对2013年1月～2019年9月解放军总医院第五医学中心曲妥珠单抗、拉帕替尼治疗失败的HER2阳性晚期乳腺癌患者进行回顾分析，其中55例口服吡咯替尼±化疗、50例注射T-DM1单药。两组患者年龄、转移数量、转移类型、转移部位分布情况基本相似，吡咯替尼组激素受体阴性占63.6%、脑转移占32.7%，T-DM1组激素受体阳性占58.0%、脑转移占20.0%。主要研究终点为无进展生存，次要终点包括客观缓解率、临床获益率、安全性。
结果，截至2019年11月1日，吡咯替尼与T-DM1相比：
无进展生存：中位6.0个月比4.2个月（95%置信区间：4.7～7.3、3.6～4.8，P=0.044）
客观缓解率：16.3%比20.0%（P=0.629）
临床获益率：45.5%比40.0%（P=0.573）
亚组分析表明，对于既往拉帕替尼治疗获益患者，吡咯替尼与T-DM1相比：
无进展生存：中位8.1个月比4.4个月（95%置信区间：4.8～11.4、3.8～5.0，P=0.013）
对于未肝转移患者，吡咯替尼与T-DM1相比：
无进展生存：中位6.9个月比4.1个月（95%置信区间：3.7～10.1、3.1～5.1，P=0.010）
吡咯替尼与T-DM1相比，主要不良事件发生率：
腹泻：98.2%比10.0%
恶心：49.1%比40.0%
血小板减少：20.0%比42.0%
3～4级不良反应：34.5%比40.0%
因此，该单中心小样本回顾研究结果表明，对于曲妥珠单抗、拉帕替尼治疗失败的HER2阳性晚期乳腺癌患者，吡咯替尼与T-DM1相比，无进展生存结局显著较好，尤其对于既往拉帕替尼治疗获益或未肝转移者，故有必要进一步开展多中心大样本前瞻随机对照研究进行验证。
Ann Transl Med. 2021 Jan;9(2):103.
Pyrotinib versus trastuzumab emtansine for HER2-positive metastatic breast cancer after previous trastuzumab and lapatinib treatment: a real-world study.
Li F, Xu F, Li J, Wang T, Bian L, Zhang S, Jiang Z.
Academy of Military Medical Sciences, Beijing, China; Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; PLA Rocket Force Characteristic Medical Center, Beijing, China.
BACKGROUND: To compare the efficacy and safety of pyrotinib and trastuzumab emtansine (T-DM1) in patients who experienced disease progression on trastuzumab and lapatinib treatment.
METHODS: This was a real-world study that included cases of metastatic breast cancer (MBC) with trastuzumab and lapatinib failure. One group of patients received pyrotinib monotherapy or combination therapy, whereas the other group received T-DM1 monotherapy. The primary study endpoint was progression-free survival (PFS); secondary endpoints were the objective response rate (ORR), clinical benefit rate (CBR) and safety.
RESULTS: Between January 2013 and November 2019, 105 patients were enrolled in the pyrotinib group (n=55) or T-DM1 group (n=50). The median PFS was 6.0 months (95% CI, 4.7 to 7.3 months) with pyrotinib and 4.2 months (95% CI, 3.6 to 4.8 months) with T-DM1 (P=0.044). ORR values were 16.3% and 20.0% in the pyrotinib and T-DM1 groups, respectively (P=0.629); CBR values were 45.5% and 40.0% in the pyrotinib and T-DM1 groups, respectively (P=0.573). Subgroup analysis of those benefitting from lapatinib revealed a median PFS of 8.1 months (95% CI, 4.8 to 11.4 months) in the pyrotinib group, whereas that of the T-DM1 group was 4.4 months (95% CI, 3.8 to 5.0 months, P=0.013). Moreover, the median PFS of patients without liver metastases was 6.9 months (95% CI, 3.7 to 10.1 months) in the pyrotinib group and 4.1 months (95% CI, 3.1 to 5.1 months) in the T-DM1 group (P=0.010). The main common adverse events (AEs) were diarrhea (98.2%) and nausea (49.1%) in the pyrotinib group and thrombocytopenia (42.0%) and nausea (40.0%) in the T-DM1 group. The percentages of grade 3 to 4 AEs in the pyrotinib and T-DM1 groups were 34.5% and 40.0%, respectively.
CONCLUSIONS: The results of this study suggest that patients with HER2-positive MBC with trastuzumab and lapatinib failure can benefit from subsequent pyrotinib treatment and tolerate this treatment well, especially those who have benefited from previous lapatinib treatment or those who have no liver metastasis.
KEYWORDS: HER2; Metastatic breast cancer (MBC); T-DM1; pyrotinib
PMID: 33569405
PMCID: PMC7867920
DOI: 10.21037/atm-20-4054
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