Genomic and immune characteristics of HER2-mutated non-small-cell lung cancer and response to immune checkpoint inhibitor-based therapy.
Genomic and immune characteristics of HER2-mutated non-small-cell lung cancer and response to immune checkpoint inhibitor-based therapy.
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人表皮生长因子受体2（HER2）突变型非小细胞肺癌的基因组与免疫特征以及对免疫检查点抑制剂疗法的反应
DOI：
10.1002/1878-0261.13439
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发表时间：
2023-08
影响因子：
6.6
通讯作者：
Wu, Yi-Long
中科院分区：
文献类型：
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作者：
Tu, Hai-Yan;Yin, Kai;Zhao, Xiaotian;Ke, E-E;Wu, Si-Pei;Li, Yang-Si;Zheng, Mei-Mei;Liu, Si-Yang Maggie;Xu, Chong-Rui;Sun, Yue-Li;Lin, Jia-Xin;Bai, Xiao-Yan;Zhang, Yi-Chen;Zhou, Qing;Yang, Jin-Ji;Zhong, Wen-Zhao;Wang, Bing-Chao;Zhang, Xu-Chao;Zhu, Dongqin;Yang, Lingling;Ou, Qiuxiang;Wu, Yi-Long
关键词：
免疫治疗在晚期HER 2突变非小细胞肺癌（NSCLC）中的疗效仍未得到全面研究。在广东省肺癌研究所共对107例HER 2新发突变NSCLC患者进行了回顾性研究[GLCI队列，20号外显子插入（ex 20 ins）：71.0%]，以比较ex 20 ins和非ex 20 ins患者的临床/分子学特征和基于免疫检查点抑制剂（ICI）的治疗疗效。两个外部队列（TCGA，n = 21; Meta，n = 30）用于验证。在GLCI队列中，68.2%的患者显示程序性死亡配体1（PD-L1）表达<1%。与ex 20 ins患者相比，非ex 20 ins患者在GLCI队列中有更多的并发突变（P < 0.01），在TCGA队列中有更高的肿瘤突变负荷（P = 0.03）。在基于ICI的治疗下，非ex 20 ins的晚期NSCLC患者的无进展生存期[中位数：13.0 vs. 3.6个月，校正风险比（HR）：0.31，95%置信区间（CI）：0.11-0.83]和总生存期可能上级（中位数：27.5 vs. 8.1个月，校正HR：0.39，95% CI：0.13-1.18），与Meta‐ICI队列的结果一致。基于ICI的治疗可作为晚期HER 2突变NSCLC的一种选择，在非ex 20 ins患者中可能具有更好的疗效。在临床实践中需要进一步的研究。 除20号外显子插入（非ex 20 ins）外，HER 2突变的HER 2突变非小细胞肺癌（NSCLC）患者的肿瘤突变负荷高于HER 2 ex 20 ins患者，但观察到相似的程序性死亡配体1表达。在基于免疫检查点抑制剂的治疗下，与HER 2 ex 20 ins患者相比，HER 2 non-ex 20 ins晚期NSCLC患者的无进展生存期和总生存期可能上级。
The efficacy of immunotherapy in advanced HER2‐mutated non‐small‐cell lung cancer (NSCLC) remains incomprehensively studied. A total of 107 NSCLC patients with de novo HER2 mutations were retrospectively studied at Guangdong Lung Cancer Institute [GLCI cohort, exon 20 insertions (ex20ins): 71.0%] to compare clinical/molecular features and immune checkpoint inhibitor (ICI)‐based therapy efficacy between patients with ex20ins and non‐ex20ins. Two external cohorts (TCGA, n = 21; META‐ICI, n = 30) were used for validation. In the GLCI cohort, 68.2% of patients displayed programmed death‐ligand 1 (PD‐L1) expression < 1%. Compared with ex20ins patients, non‐ex20ins patients had more concurrent mutations in the GLCI cohort (P < 0.01) and a higher tumour mutation burden in the TCGA cohort (P = 0.03). Under ICI‐based therapy, advanced NSCLC patients with non‐ex20ins had potentially superior progression‐free survival [median: 13.0 vs. 3.6 months, adjusted hazard ratio (HR): 0.31, 95% confidence interval (CI): 0.11–0.83] and overall survival (median: 27.5 vs. 8.1 months, adjusted HR: 0.39, 95% CI: 0.13–1.18) to ex20ins patients, consistent with findings in the META‐ICI cohort. ICI‐based therapy may serve as an option for advanced HER2‐mutated NSCLC, with potentially better efficacy in non‐ex20ins patients. Further investigations are warranted in clinical practice. HER2‐mutated non‐small‐cell lung cancer (NSCLC) patients with HER2 mutations other than exon 20 insertions (non‐ex20ins) had higher tumour mutation burden than patients with HER2 ex20ins, whereas similar programmed death‐ligand 1 expression was observed. Under immune checkpoint inhibitor‐based therapy, advanced NSCLC patients with HER2 non‐ex20ins had potentially superior progression‐free survival and overall survival compared with patients with HER2 ex20ins.
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影响因子：
4.7
作者：
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DOI：
10.1158/1078-0432.ccr-12-0912
发表时间：
2012-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
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影响因子：
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影响因子：
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通讯作者：
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