吡咯替尼与乳腺癌脑转移患者总生存
HER2阳性晚期乳腺癌预后较差，而且容易发生脑转移。随机对照研究结果表明，HER1、HER2、HER4酪氨酸酶抑制剂吡咯替尼对于HER2阳性晚期乳腺癌患者的抗肿瘤活性令人鼓舞，可显著改善无进展生存。不过，根据真实世界数据分析吡咯替尼是否影响总生存的研究仍然很少。
2021年6月10月，美国癌症研究协会《临床癌症研究》在线发表中南大学湘雅二医院、中南大学湘雅医院、湖南省肿瘤医院暨中南大学湘雅医学院附属肿瘤医院、湖南省人民医院暨湖南师范大学第一附属医院、中南大学湘雅三医院、湖南中医药大学第一附属医院、株洲市中心医院暨中南大学湘雅医学院附属株洲医院、永州市第三人民医院、岳阳市第一人民医院、湘潭市第一人民医院暨湘潭市肿瘤医院、常德市第三人民医院、湘潭市中心医院、邵阳市中心医院、邵阳市中医院、常德市第一人民医院、湖南省直中医医院暨湖南中医药大学第三附属医院暨湖南中医药高等专科学校附属第一医院、益阳市中心医院、郴州市第一人民医院、湘潭县人民医院的真实世界研究报告，对吡咯替尼治疗HER2阳性晚期乳腺癌患者的多中心数据进行了最终分析。
前情提要
该多中心回顾研究对2018年6月～2019年8月湖南省20家医院采用吡咯替尼治疗168例HER2阳性晚期乳腺癌患者的无进展生存、总生存、临床获益率、总体缓解率、肿瘤突变负荷进行最终分析，并对脑转移患者进行探索性分析。
结果，中位随访18.5个月：
全部168例患者
无进展生存：中位8.00个月
总生存时间：中位19.07个月
39例脑转移患者
无进展生存：中位8.67个月
总生存时间：中位13.93个月
对于脑转移患者，手术/放疗组与未手术/未放疗组相比：
无进展生存：中位9.97个月比7.73个月（P=0.19）
总生存时间：中位20.67个月比12.43个月（P=0.021）
临床获益率：58.6%比41.4%
总体缓解率：24.1%比31.0%
肿瘤突变负荷较高与较低的患者相比：
无进展生存：中位8.2个月比22.87个月（P=0.0028）
总生存时间：中位4.9个月比13.44个月（P=0.0072）
因此，该小样本回顾研究结果表明，吡咯替尼治疗HER2阳性晚期乳腺癌脑转移效果令人鼓舞，故有必要进一步开展大样本前瞻对照研究进行验证。对于该队列脑转移患者，手术或放疗联合吡咯替尼可显著延长总生存。肿瘤突变负荷可能是预测无进展生存和总生存的探索性生物标志，其临床应用仍需进一步验证。
Clin Cancer Res. 2021 Jun 10. Online ahead of print.
Pyrotinib treatment in patients with HER2-positive metastatic breast cancer and brain metastasis: exploratory final analysis of real-world, multicenter data.
Anwar M, Chen Q, Ouyang D, Wang S, Xie N, Ouyang Q, Fan P, Qian L, Chen G, Zhou E, Guo L, Gu X, Ding B, Yang X, Liu L, Deng C, Xiao Z, Li J, Wang Y, Zeng S, Hu J, Zhou W, Qiu B, Wang Z, Weng J, Liu M, Li Y, Tang T, Wang J, Zhang H, Dai B, Tang W, Wu T, Xiao M, Li X, Liu H, Li L, Yi W.
The Second Xiangya Hospital of Central South University; Xiangya Hospital Central South University; Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University; Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University); The Third XIANGYA Hospital of Central South University; The First Hospital of Hunan University of Chinese Medicine; The Affiliated ZhuZhou Hospital of Xiangya School of Medicine CSU; The Third People's Hospital of Yongzhou; The First People's Hospital of Yueyang; The First People's Hospital of Xiangtan City; The Third People's Hospital of Changde; The Central Hospital of Xiangtan; The Central Hospital of Shaoyang; Shaoyang Hospital of Traditional Chinese Medicine; The First People's Hospital of Changde; The Third Hospital of Hunan University of Chinese Medicine (The Third Affiliated Hospital of Hunan junior college of Chinese Medicine); Yiyang Central Hospital; The First People's Hospital of Chenzhou; The People's Hospital of Xiangtan County.
PURPOSE: Patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC patients to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce.
EXPERIMENTAL DESIGN: This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2+ MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR) and overall response rate (ORR) were analyzed.
RESULTS: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR).
CONCLUSION: Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.
PMID: 34112711
DOI: 10.1158/1078-0432.CCR-21-0474