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脑转移是HER2阳性晚期乳腺癌患者的常见死亡原因。目前，乳腺癌伴脑转移主要采用全脑放疗。吡咯替尼是HER1、HER2、HER4的不可逆抑制剂，初期研究已经表明其抗肿瘤活性令人鼓舞、耐受性可接受。 2021年8月16日，英国《抗癌药物》在线发表中国人民解放军陆军军医大学大坪医院的研究报告，探讨了吡咯替尼＋全脑放疗对HER2阳性晚期乳腺癌伴脑转移患者的效果。 该单中心随机对照研究于2015～2019年入组HER2阳性晚期乳腺癌伴脑转移全脑放疗患者20例，按1∶1的比例随机分为吡咯替尼＋卡培他滨组10例、卡培他滨组10例。主要终点为总缓解率，次要终点包括无进展生存、总生存。 结果，吡咯替尼＋卡培他滨组与卡培他滨组相比： 随访时间：中位15.8比14.9个月（四分位：10.5～17.8、10.0～16.8） 一线治疗：4比4例 二线治疗：3比3例 三线治疗：3比3例 总缓解率：80%比40%（P<0.0001） 无进展生存：中位18.5个月比6.5个月（P<0.0001） 进展时间：中位20个月比7.5个月（P<0.0001） 缓解时间：中位16.5个月比8.5个月（P<0.0001） 总生存：未达终点
此外，吡咯替尼还可增强体外培养HER2阳性晚期乳腺癌细胞系的放疗敏感性。 因此，该单中心小样本随机对照研究结果表明，口服吡咯替尼联合全脑放疗可显著提高HER2阳性晚期乳腺癌伴脑转移患者的总缓解率、无进展生存、进展时间和缓解时间，并未引起额外不良事件，还可有效提高HER2阳性晚期乳腺癌伴脑转移患者的肿瘤放疗敏感性。 Anticancer Drugs. 2021 Aug 16. Online ahead of print. Pyrotinib treatment enhances the radiosensitivity in HER2-positive brain metastatic breast cancer patients. Tian W, Hao S, Wang L, Chen Y, Li Z, Luo D. Daping Hospital, Army Medical University, Chongqing, China. Brain metastasis is a common cause of death in HER2-positive breast cancer patients. Currently, it is mainly treated by whole-brain radiotherapy. Pyrotinib is an irreversible pan-ErbB inhibitor, which has demonstrated promising tumor-suppressing activity and acceptable tolerance in previous phase trials. In the present study, we evaluated the efficacy of pyrotinib on HER2-positive brain metastatic breast cancer patients treated with whole-brain radiotherapy. A total of 20 such patients were separated into pyrotinib plus capecitabine and capecitabine-only groups in a 1:1 ratio. All patients met either the primary or secondary endpoints. Oral admission of pyrotinib together with radiotherapy can significantly increase the overall response rate, progression-free survival, time to progression and duration of response of HER2+ brain metastatic breast cancer patients, without causing extra adverse events. In addition, pyrotinib can enhance the radiosensitivity of in-vitro cultured HER2+ breast cancer cell lines. The outcome of our study suggests that pyrotinib might be an effective medication to enhance the tumor radiosensitivity of HER2-positive brain metastatic breast cancer patients. PMID: 34407046 DOI: 10.1097/CAD.0000000000001199 
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