拉帕替尼失败后吡咯替尼是否有效
吡咯替尼是中国原创的人类表皮生长因子受体（HER1、HER2、HER4）酪氨酸激酶不可逆抑制剂，对于HER2阳性晚期乳腺癌，已被随机对照研究证实显著优于拉帕替尼。不过，对于拉帕替尼治疗失败后的HER2阳性晚期乳腺癌，吡咯替尼有否有效？由于既往证据极少，故仍然存在争议。
2021年8月26日，瑞士《药理学前沿》在线发表中南大学湘雅二医院、中南大学湘雅医院、中南大学湘雅医学院附属肿瘤医院、湖南省人民医院、中南大学湘雅三医院的真实世界研究报告，比较了吡咯替尼至少三线治疗对HER2阳性晚期乳腺癌已经或未经拉帕替尼治疗患者的有效性。
该多中心回顾研究对2018年6月～2019年8月接受吡咯替尼至少三线线治疗的94例HER2阳性晚期乳腺癌患者进行回顾分析，其中已经、未经拉帕替尼治疗的患者分别为30例（31.9%）、64例（68.1%）。主要和次要终点分别为总生存和无进展生存。由于已经、未经拉帕替尼治疗的患者数量和特征相差悬殊，故采用倾向评分匹配和逆向概率加权对两组患者的重要特征进行平衡。
结果，未经与已经拉帕替尼治疗的患者相比：
原始队列
无进展生存：9.02比6.36个月（P=0.05）
总生存：20.73比14.35个月（P=0.08）
倾向评分匹配队列
无进展生存：9.02比6.08个月（P=0.07）
总生存：19.07与18.00个月（P=0.61）
逆向概率加权队列
无进展生存：9.90比6.17个月（P=0.05）
总生存：19.53比15.10个月（P=0.08）
亚组分析表明，对于绝经前亚组和未经曲妥珠单抗治疗亚组，未经与已经拉帕替尼治疗的患者相比，无进展生存可见显著差异，总生存未见显著差异。
因此，该真实世界多中心小样本回顾研究结果表明，吡咯替尼对HER2阳性晚期乳腺癌患者的效果令人鼓舞，尤其未经拉帕替尼治疗、绝经前和未经曲妥珠单抗治疗的患者，并且对已经拉帕替尼治疗的患者也有一些效果，故有必要进一步开展多中心大样本前瞻研究进行验证。
Front Pharmacol. 2021 Aug 26;12:682568.
The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study.
Ouyang DJ, Chen QT, Anwar M, Xie N, Ouyang QC, Fan PZ, Qian LY, Chen GN, Zhou EX, Guo L, Gu XW, Ding BN, Yang XH, Liu LP, Deng C, Xiao Z, Li J, Wang YQ, Zeng S, Wang S, Yi W.
The Second Xiangya Hospital, Central South University, Changsha, China; Xiangya Hospital, Central South University, Changsha, China; The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China; Hunan Provincial People's Hospital, Changsha, China; The Third Xiangya Hospital, Central South University, Changsha, China.
BACKGROUND: Pyrotinib is a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor. Evidence of the efficacy of pyrotinib-based treatments for HER2-positive metastatic breast cancer (MBC) in patients exposed to lapatinib is limited.
METHODS: Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC were included in this retrospective study. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were implemented to balance important patient characteristics between groups.
RESULTS: Thirty (31.9%) patients were pretreated with lapatinib and subsequently received pyrotinib as an anti-HER2 treatment, and 64 (68.1%) patients did not receive this treatment. The OS and PFS indicated a beneficial trend in lapatinib-naive group compared to lapatinib-treated group in either the original cohort (PFS: 9.02 vs 6.36 months, P = 0.05; OS: 20.73 vs 14.35 months, P = 0.08) or the PSM (PFS: 9.02 vs 6.08 months, P = 0.07; OS: 19.07 vs 18.00 months, P = 0.61) or IPTW (PFS: 9.90 vs 6.17 months, P = 0.05; OS: 19.53 vs 15.10 months, P = 0.08) cohorts. Subgroup analyses demonstrated lapatinib treatment-related differences in PFS in the premenopausal subgroup and the no prior trastuzumab treatment subgroup, but no significant differences were observed in OS.
CONCLUSION: Pyrotinib-based therapy demonstrated promising effects in HER2-positive MBC patients in a real-world study, especially in lapatinib-naive patients, and also some activity in lapatinib-treated patients.
KEYWORDS: HER2 breast cancer; lapatinib-naive; lapatinib-treated; metastases; pyrotinib
PMID: 34512325
PMCID: PMC8428978
DOI: 10.3389/fphar.2021.682568