HER2阳性晚期乳腺癌：吡咯替尼＋长春瑞滨优于拉帕替尼＋卡培他滨
吡咯替尼是中国原创的HER1、HER2、HER4酪氨酸激酶不可逆抑制剂，对于HER2阳性乳腺癌具有良好的疗效。随机对照三期临床PHOEBE研究已经证实，吡咯替尼＋卡培他滨与拉帕替尼＋卡培他滨相比，无进展生存显著较好。口服长春瑞滨也通常被用于联合抗HER2治疗。不过，吡咯替尼＋长春瑞滨与拉帕替尼＋卡培他滨相比，关于实际用药情况、安全性和有效性的临床证据极少。
2021年8月5日，瑞士《肿瘤学前沿》在线发表复旦大学附属肿瘤医院谢一兆、李懿、王碧芸、四川大学华西医院罗婷、北京三环肿瘤医院桑蝶、中国医学科学院肿瘤医院袁芃、江苏省人民医院李薇、山东省肿瘤医院李慧慧、复旦大学附属华东医院葛睿等学者的YOUNGBC-14研究报告，对吡咯替尼＋长春瑞滨、拉帕替尼＋卡培他滨治疗HER2阳性晚期乳腺癌患者的实际用药情况、安全性和有效性进行了比较。
YOUNGBC-14 (NCT04850625): Pyrotinib Plus Vinorelbine Versus Lapatinib Plus Capecitabine in Patients With Previously Treated HER2-Positive Metastatic Breast Cancer: a Multicenter, Retrospective Study
该多中心回顾研究对2015年6月～2021年1月在复旦大学附属肿瘤医院、四川大学华西医院、北京三环肿瘤医院、中国医学科学院肿瘤医院、江苏省人民医院接受吡咯替尼＋长春瑞滨或拉帕替尼＋卡培他滨治疗的HER2阳性晚期乳腺癌曲妥珠单抗和紫杉类治疗失败患者医疗记录进行回顾分析。
结果，共计224例患者，其中132例（58.9%）患者接受拉帕替尼＋卡培他滨，92例（41.1%）患者接受吡咯替尼＋长春瑞滨。
吡咯替尼＋长春瑞滨组与拉帕替尼＋卡培他滨组相比：
基线特征相似
中位无进展生存显著较长：8.3个月比5.0个月（风险比：0.47，95%置信区间：0.34～0.65，P<0.001）
曲妥珠单抗耐药患者中位无进展生存显著较长：9.6个月比5.0个月（风险比：0.30，95%置信区间：0.16～0.57，P<0.001）
曲妥珠单抗无效患者中位无进展生存显著较长：6.3个月比5.0个月（风险比：0.58, 95%置信区间：0.39～0.86，P=0.004）
腹泻率较高：23.9%比8.3%
停药率相似：9.8%比7.8%
因此，该多中心小样本回顾研究结果表明，对于中国HER2阳性晚期乳腺癌曲妥珠单抗治疗失败患者，吡咯替尼＋长春瑞滨与拉帕替尼＋卡培他滨相比，实际用药比例相对较低，无论曲妥珠单抗是否耐药，中位无进展生存时间都显著较长，虽然腹泻率较高，但是停药率相似。
相关链接
Front Oncol. 2021 Aug 5;11:699333.
Pyrotinib Plus Vinorelbine Versus Lapatinib Plus Capecitabine in Patients With Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Retrospective Study.
Xie Y, Li Y, Ting L, Sang D, Yuan P, Li W, Li H, Ge R, Wang B.
Fudan University Shanghai Cancer Center, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China; Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China; West China Hospital, Sichuan University, Sichuan, China; San Huan Cancer Hospital, Beijing, China; National Cancer Center, Tumor Hospital of the Chinese Academy of Medical Sciences, Beijing, China; Jiangsu Province Hospital, Nanjing, China; Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China; Huadong Hospital Affiliated to Fudan University, Shanghai, China.
BACKGROUND: Pyrotinib is a newly-developed irreversible pan-ErbB (erythroblastic leukemia viral oncogene homolog) receptor oral tyrosine kinase inhibitor (TKI) with promising efficacy in the human epidermal growth factor receptor-2 (HER2) positive breast cancer. The phase III PHOEBE study proved that pyrotinib plus capecitabine exceeded lapatinib plus capecitabine (LX) in PFS (p < 0.001). Oral vinorelbine is commonly used in combination with anti-HER2 treatment. However, no evidence was reported in terms of the real-world pattern, safety, and efficacy of pyrotinib plus vinorelbine (NP) compared with LX.
METHODS: Medical records were retrospectively evaluated for all HER2-positive metastatic breast cancer (MBC) patients who experienced progression on prior trastuzumab-containing regimens (advanced setting) and taxane (any setting) and received NP or LX therapy from 2015 to 2021 in five institutions.
RESULTS: A total of 224 patients were enrolled and evaluated, of which 132 (58.9%) patients received LX and 92 (41.1%) patients received NP. The median progression-free survival (mPFS) of NP group was significantly longer than that in LX group (8.3 vs 5.0 months, HR = 0.47 95% CI 0.34-0.65, p < 0.001). The advantage of NP over LX was seen both in patients with trastuzumab resistance (p < 0.001) and refractoriness (p = 0.004). The NP group had more diarrhea cases (23.9%) compared to the LX group (8.3%). Discontinuation rates in the two groups were similar.
CONCLUSIONS: This trial revealed the clinical practice of NP and LX treatment among HER2+ MBC patients pretreated with trastuzumab in China. More patients received LX than NP in real-world while the efficacy of NP exceeded LX in terms of PFS regardless of resistant status of trastuzumab. Although the NP group had more diarrhea cases, toxicities in both groups were acceptable.
KEYWORDS: HER2; breast cancer; combined therapy; metastatic; pyrotinib
PMID: 34422652
PMCID: PMC8374067
DOI: 10.3389/fonc.2021.699333