晚期HER2突变非小细胞肺癌对吡咯替尼反应的分子相关性：两项II期试验的生物标志物分析
Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials.
作者信息
Mao Shiqi, Yang Shuo, Liu Xinyu, Li Xingya, Wang Qiming, Zhang Yiping, Chen Jianhua, Wang Yan, Gao Guanghui, Wu Fengying, Jiang Tao, Zhang Jiao, Yang Ying, Lin Xiang, Zhu Xiaoyu, Zhou Caicun, Ren Shengxiang
机构信息
Department of Medical Oncology, Shanghai Pulmonary Hospital, Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, China.
Second Ward of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
出版信息
Exp Hematol Oncol. 2023 Jun 9;12(1):53. doi: 10.1186/s40164-023-00417-y.
BACKGROUND
Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation.
METHODS
Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated.
RESULTS
This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p < 0.001) than those with mutations. ctDNA of nonshedding and clearance exhibited significantly longer PFS (median: 10.2 vs. 9.8 vs. 5.6 months, p = 0.036) and a trend of longer OS (median: 35.3 vs. 18.1 vs. 14.6 months, p = 0.357) than those not.
CONCLUSION
Patients with TP53 wild type, ctDNA nonshedding, or clearance showed superior efficacy of pyrotinib in patients with HER2-mutated advanced NSCLC, which might be helpful to guide the utility of pyrotinib in clinical setting.
TRIAL REGISTRATION
The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936).
背景
伴有HER2突变的非小细胞肺癌（NSCLC）已进入靶向治疗时代。然而，抗HER2抗体药物偶联物（ADC）和酪氨酸激酶抑制剂（TKI）均显示出中等的客观缓解率（ORR）和中位无进展生存期（PFS）。本研究旨在探讨HER2突变的晚期NSCLC患者对吡咯替尼反应者的分子特征。
方法
对我们之前两项II期试验的患者进行汇总分析。通过下一代测序（NGS）检测他们的循环肿瘤DNA（ctDNA），并研究其与吡咯替尼疗效的相关性。
结果
该汇总分析纳入75例患者，其中50例有基线血浆样本最终纳入，中位年龄57岁。总体ORR和中位PFS分别为28%和7.0个月。生物标志物分析显示，5例患者ctDNA未脱落。TP53野生型患者的疾病控制率（97.1%对68.8%，p = 0.010）、PFS（中位8.4对2.8个月，p = 0.001）和总生存期（OS，中位26.7对10.4个月，p < 0.001）显著高于有突变的患者。ctDNA未脱落和清除的患者的PFS显著更长（中位：10.2对9.8对5.6个月，p = 0.036），OS有延长趋势（中位：35.3对18.1对14.6个月，p = 0.357）。
结论
TP53野生型、ctDNA未脱落或清除的患者在HER2突变的晚期NSCLC患者中显示出吡咯替尼的疗效更佳，这可能有助于指导吡咯替尼在临床中的应用。
试验注册
患者来自两项注册临床试验（ClinicalTrials.gov：NCT02535507，NCT02834936）。
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