Genomic and immune characteristics of HER2-mutated non-small-cell lung cancer and response to immune checkpoint inhibitor-based therapy

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^*

来源：Molecular Oncology, 2023, 17(8): 1581-1594.

DOI：10.1002/1878-0261.13439

• advanced NSCLC
• exon 20 insertion
• human epidermal growth factor receptor 2
• immune checkpoint inhibitor
• non-exon 20 insertion

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.

• 单位
  1; 广东省人民医院; 南方医科大学