Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits.
Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits.
复制标题
基于吡咯替尼治疗 HER2 阳性晚期乳腺癌脑转移患者的真实世界数据：单中心回顾性分析和分子肖像
DOI：
10.3389/fonc.2023.1105474
复制
发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
吡咯替尼是一种新型的不可逆的泛HER酪氨酸激酶抑制剂（TKI）。然而，含吡咯替尼治疗人表皮生长因子受体2（HER 2）阳性转移性乳腺癌（MBC）和脑转移（BM）的真实数据有限，该亚群的基因组谱几乎不确定。方法和材料本分析纳入接受含吡咯替尼治疗的HER 2阳性MBC BM患者（n = 35）。评价了无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）和毒性特征。使用考克斯比例风险模型估计疾病进展的风险比（HR）和95%置信区间（CI）。对来自BM和无BM患者的血浆和原发性乳腺肿瘤进行了618个癌症相关基因的靶向下一代测序。结果中位PFS为8.00（95% CI，5.98-10.017）个月，中位OS为23（95% CI，10.412-35.588）个月。ORR为45.7%，DCR为74.3%。在考克斯多变量分析中，既往暴露于脑放疗（HR = 3.268）、接受吡咯替尼作为三线或更高线治疗（HR = 4.949）、幕下脑转移（HR = 6.222）以及幕上和幕下脑转移（HR = 5.863）与进展风险增加独立相关。常见的3-4级不良事件为直接胆红素升高（14.3%），2例患者发生3-4级腹泻。在探索性基因组分析中，BM组中FGFR 3、CD 276、CDC 73和EPHX 1的改变频率较高。BM组中血浆和原发性病变突变谱的一致性显著较低（30.4% vs. 65.5%; p = 0.0038）。结论：含吡咯替尼的治疗在HER 2阳性MBC的BM患者中显示出良好的有效性和可耐受的安全性，特别是在脑放疗初治、接受吡咯替尼作为一线或二线治疗并发生幕上脑转移的人群中。在探索性基因组分析中，BM患者显示出与无BM患者不同的基因组特征。
Introduction Pyrotinib is a novel irreversible pan-HER tyrosine kinase inhibitor (TKI). However, real-world data of pyrotinib-containing therapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and developing brain metastases (BMs) are limited, and the genomic profile of this subpopulation is almost undefined. Methods and materials Patients with BM of HER2-positive MBC (n = 35) treated with pyrotinib-containing therapy were enrolled in this analysis. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) for disease progression were estimated using the Cox proportional hazards models. Targeted next-generation sequencing of 618 cancer-relevant genes was performed on plasma and primary breast tumors from patients with BM and without BM. Results The median PFS time was 8.00 (95% CI, 5.98–10.017) months, and the median OS time was 23 (95% CI, 10.412–35.588) months. The ORR was 45.7%, and the DCR was 74.3%. In the Cox multivariate analysis, prior exposure to brain radiotherapy (HR = 3.268), received pyrotinib as third- or higher-line treatment (HR = 4.949), subtentorial brain metastasis (HR = 6.222), and both supratentorial and subtentorial brain metastases (HR = 5.863) were independently associated with increased risk of progression. The frequent grade 3–4 adverse event was increased direct bilirubin (14.3%), and two patients suffered from grade 3–4 diarrhea. In the exploratory genomic analysis, altered frequencies of FGFR3, CD276, CDC73, and EPHX1 were higher in the BM group. The consistency of mutated profiles of plasma and primary lesion in the BM group was significantly lower (30.4% vs. 65.5%; p = 0.0038). Conclusions Pyrotinib-containing therapy shows favorable effectiveness and tolerable safety in patients with BM of HER2-positive MBC, particularly in a population that is brain radiotherapy-naïve, received pyrotinib as first- or second-line treatment, and developed supratentorial brain metastasis. In the exploratory genomic analysis, patients with BM showed distinct genomic features from patients without BM.
登录
查看更多内容
影响因子：
5.8
作者：
Huang, Richard S. P.;Haberberger, James;Ramkissoon, Shakti H.
通讯作者：
Ramkissoon, Shakti H.
影响因子：
50.5
作者：
Burstein, HJ;Lieberman, G;Klein, P
通讯作者：
Klein, P
影响因子：
51.1
作者：
Bachelot, Thomas;Romieu, Gilles;Labbe-Devilliers, Catherine
通讯作者：
Labbe-Devilliers, Catherine
影响因子：
50.5
作者：
Curigliano, G.;Mueller, V;Winer, E.
通讯作者：
Winer, E.
影响因子：
45.3
作者：
Freedman, Rachel A.;Gelman, Rebecca S.;Lin, Nancy U.
通讯作者：
Lin, Nancy U.