中国晚期乳腺癌吡咯替尼真实疗效
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，已被随机对照研究证实对HER2阳性晚期乳腺癌具有良好的抗癌效果和可接受的安全性。不过，随机对照研究入组患者大多未接受过恩美曲妥珠单抗或拉帕替尼治疗。
2021年9月14日，英国德孚《癌症管理与研究》在线发表山东大学齐鲁医院、山东大学齐鲁医院青岛分院、菏泽市立医院、浙江省人民医院的真实世界研究报告，回顾分析了吡咯替尼对HER2阳性晚期乳腺癌患者的有效性和安全性。
该多中心回顾研究对2018年8月～2019年7月山东大学齐鲁医院和中国山东省其他医疗中心吡咯替尼治疗HER2阳性晚期乳腺癌患者的真实世界临床病理和治疗数据进行回顾分析。
结果，64例患者被纳入分析，中位随访260天（四分位：199.0～339.0天）。其中59例（92.2%）患者既往曾接受过曲妥珠单抗和/或恩美曲妥珠单抗治疗、11例（17.2%）患者曾接受过拉帕替尼治疗。
全部患者的客观缓解率为73.4%、疾病控制率为98.4%、临床获益率为87.5%。
曾接受过与未接受过拉帕替尼的患者相比，客观缓解率：44.1%比77.5%（P=0.037）。单因素逻辑回归分析表明，拉帕替尼用药史与吡咯替尼治疗客观缓解率成反比（比值比：0.248，95%置信区间：0.063～0.970，P=0.045）。
既往拉帕替尼用药患者、内脏转移患者的中位无进展生存分别为299天和359天（95%置信区间：240.1～357.9、258.3～459.7），但是直至截止日期整个队列无进展生存才达到中位。
多因素比例风险回归分析表明，无进展生存显著较短的独立预测因素为内脏转移（P=0.041），而非拉帕替尼用药史（P=0.092）。
吡咯替尼治疗相关3级不良事件发生率前三位：腹泻（28.1%）、手足综合征（17.2%）、中性粒细胞减少（9.4%）。
因此，该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客观缓解率、疾病控制率、临床获益率较高，甚至对既往接受过拉帕替尼的患者。吡咯替尼是拉帕替尼的有效替代药品，不良反应可以耐受并且容易控制。
Cancer Manag Res. 2021 Sep 14;13:7165-7174.
Real-World Analysis of the Efficacy and Safety of a Novel Irreversible HER2 Tyrosine Kinase Inhibitor Pyrotinib in Patients with HER2-Positive Metastatic Breast Cancer.
Sun Y, Chen B, Li J, Peng L, Li S, Yu X, Li L.
School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, China; Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Heze Municipal Hospital, Heze, Shandong, China; Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
BACKGROUND: As a novel irreversible pan-ErbB inhibitor recently approved in China, pyrotinib has exhibited promising anticancer efficacy and acceptable safety profile in HER2-positive metastatic breast cancer (mBC). The aim of this retrospective study was to estimate the efficacy and safety of pyrotinib treatment in Chinese mBC patients.
METHODS: We retrospectively reviewed the real-world clinicopathological and treatment data of HER2-positive mBC patients receiving pyrotinib-based treatment from August 2018 to July 2019 in Qilu Hospital of Shandong University and other medical centers of Shandong Province in China.
RESULTS: A total of 64 patients treated with pyrotinib were included for analysis, and the median follow-up duration was 260 days (interquartile range, 199.0 to 339.0 days). Fifty-nine (92.2%) patients had been previously treated with trastuzumab and/or T-DM1, while 11 (17.2%) patients had been exposed to lapatinib. The objective response rate (ORR) of all patients was 73.4%, and the disease control rate (DCR) was 98.4%, with a clinical benefit rate (CBR) of 87.5%. Patients with exposure to lapatinib responded well to pyrotinib-based treatment, although the ORR was significantly lower compared with that of patients without exposure to lapatinib (44.1% vs 77.5%, p=0.037). Previous lapatinib exposure was negatively associated with the objective response of pyrotinib treatment (odds ratio [OR]=0.248, 95% confidence interval [CI] 0.063-0.970, p=0.045). The median progression-free survival (mPFS) for patients with previous lapatinib exposure and patients with visceral metastasis was 299 days (95% CI 240.1-357.9 days) and 359 days (95% CI 258.3-459.7 days), respectively. But the mPFS of the whole cohort has not been reached until the cut-off date. Cox multivariate analysis revealed that only visceral metastasis was an independent predictor of significantly shorter PFS (p=0.041) but not previous exposure to lapatinib (p=0.092). Diarrhea (28.1%), hand-foot syndrome (17.2%), and neutropenia (9.4%) were the most common grade 3 adverse events associated with pyrotinib treatment.
CONCLUSION: Pyrotinib is highly beneficial to HER2-positive metastatic breast cancer patients, even in patients with previous lapatinib exposure. Pyrotinib is a feasible replacement of lapatinib in combination with chemotherapeutic drugs or as a monotherapy. Adverse effects are tolerable and easily manageable.
KEYWORDS: HER2 positive; adverse effect; breast cancer; objective response rate; pyrotinib
PMID: 34548820
PMCID: PMC8449550
DOI: 10.2147/CMAR.S321428