Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China; Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, China.
Department of Respiratory and Critical Care Medicine, Hebei Petrochina Central Hospital, Langfang, China.
Eur J Cancer. 2023 Jul;188:81-89. doi: 10.1016/j.ejca.2023.04.009. Epub 2023 Apr 20.
Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation generally respond well to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). However, genomic characterisation of de novo EGFR copy number gain (CNG) and its impact on the efficacy of first-line EGFR-TKIs remains unclear.
This multicenter, retrospective and real-world study included two cohorts that enroled EGFR mutant NSCLC patients. EGFR CNG was tested by next-generation sequencing of untreated tissue specimens. Cohort 1 detected the impact of EGFR CNG on first-line EGFR-TKIs treatment, and cohort 2 explored the genomic characterisation.
Cohort 1 enroled 355 patients from four cancer centres between January 2013 and March 2022. The patients were divided into three groups, included the EGFR non-CNG, EGFR CNG, and EGFR uncertain-CNG. No significant difference in progression-free survival (PFS) was found between the three groups (10.0 months vs. 10.8 months vs. 9.9 months, respectively, p = 0.384). Furthermore, the overall response rate was not statistically significant in the EGFR CNG group compared to the EGFR non-CNG or uncertain arm (70.3% vs. 63.2% vs. 54.5%, respectively, p = 0.154). Cohort 2 included 7876 NSCLC patients with 16.4% showing EGFR CNG. Gene mutations such as TP53, IKZF1, RAC1, MYC, MET, CDKN2A/B and alterations of the metabolic-related and ERK signalling pathway were significantly associated with patients with EGFR CNG compared to those without.
De novo EGFR CNG had no effect on the efficacy of first-line EGFR-TKI treatment in EGFR mutant NSCLC patients, and tumours with EGFR CNG had more complex genomic profiles than those without.
表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者通常对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）反应良好。然而，EGFR 拷贝数获得（CNG）的基因组特征及其对一线 EGFR-TKI 疗效的影响尚不清楚。
本多中心、回顾性和真实世界研究包括两个队列，入组 EGFR 突变 NSCLC 患者。通过下一代测序检测未经治疗的组织标本中 EGFR CNG。队列 1 检测 EGFR CNG 对一线 EGFR-TKI 治疗的影响，队列 2 则探索基因组特征。
队列 1 纳入了 2013 年 1 月至 2022 年 3 月期间四个癌症中心的 355 名患者。患者分为三组，包括 EGFR 非 CNG、EGFR CNG 和 EGFR 不确定 CNG。三组之间的无进展生存期（PFS）无显著差异（分别为 10.0 个月、10.8 个月和 9.9 个月，p=0.384）。此外，EGFR CNG 组的总缓解率与 EGFR 非 CNG 或不确定组相比无统计学意义（分别为 70.3%、63.2%和 54.5%，p=0.154）。队列 2 纳入了 7876 名 NSCLC 患者，其中 16.4%存在 EGFR CNG。与无 EGFR CNG 的患者相比，EGFR CNG 患者的基因突变更为复杂，如 TP53、IKZF1、RAC1、MYC、MET、CDKN2A/B 和代谢相关及 ERK 信号通路的改变。
新发 EGFR CNG 对 EGFR 突变 NSCLC 患者一线 EGFR-TKI 治疗的疗效无影响，而存在 EGFR CNG 的肿瘤具有比无 EGFR CNG 的肿瘤更为复杂的基因组图谱。
