Abstract：
BACKGROUND: Epidermal growth factor receptor (EGFR) amplification refers to the copy number increase of EGFR gene, and is often identified as a \"bypass\" way of Epidermal growth factor receptor Tyrosine kinase inhibitors (EGFR-TKI) resistance. We aimed to explore the effect of EGFR amplification on EGFR mutation treatment-naive advanced non-squamous non-small cell lung cancer (NSCLC) patients.
METHODS: We conducted a prospective observational study in single center, enrolling advanced non-squamous NSCLC patients receiving Tyrosine kinase inhibitors (TKIs) between March 3, 2019, and February 1, 2022. Next-generation sequencing (NGS) was used to detect genetic alterations in tumor tissue samples. Progression-free survival (PFS) curves were performed using the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate factors affecting the efficacy of TKIs.
RESULTS: A total of 117 treatment-naive advanced NSCLC patients were identified in this study. EGFR amplification was found in 22 of 117 (18.8%) patients with EGFR mutations. Of 22 patients with EGFR amplification, 10 patients harbored EGFR 19 del, 11 patients with 21-L858R. The median follow-up time was 22.47 months. The median PFS of the patients with or without EGFR amplification was 8.25 months and 10.67 months, respectively (log-rank test, P = 0.63). In multivariate analysis, EGFR amplification was not an independent prognosis factor for the patients receiving first-line TKIs [HR = 1.38, 95%CI (0.73-2.58), P = 0.321]. Subgroup analysis revealed that EGFR amplification is a risk factor for progression in the brain metastasis population. [HR = 2.28, 95%CI (1.01, 5.14), P = 0.047].
CONCLUSIONS: EGFR amplification is not an independent prognosis factor for PFS in advanced non-squamous NSCLC patients receiving first-line TKIs. However, it is an independent risk factor for PFS in the brain metastasis population.
METHODS: We conducted a prospective observational study in single center, enrolling advanced non-squamous NSCLC patients receiving Tyrosine kinase inhibitors (TKIs) between March 3, 2019, and February 1, 2022. Next-generation sequencing (NGS) was used to detect genetic alterations in tumor tissue samples. Progression-free survival (PFS) curves were performed using the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate factors affecting the efficacy of TKIs.
RESULTS: A total of 117 treatment-naive advanced NSCLC patients were identified in this study. EGFR amplification was found in 22 of 117 (18.8%) patients with EGFR mutations. Of 22 patients with EGFR amplification, 10 patients harbored EGFR 19 del, 11 patients with 21-L858R. The median follow-up time was 22.47 months. The median PFS of the patients with or without EGFR amplification was 8.25 months and 10.67 months, respectively (log-rank test, P = 0.63). In multivariate analysis, EGFR amplification was not an independent prognosis factor for the patients receiving first-line TKIs [HR = 1.38, 95%CI (0.73-2.58), P = 0.321]. Subgroup analysis revealed that EGFR amplification is a risk factor for progression in the brain metastasis population. [HR = 2.28, 95%CI (1.01, 5.14), P = 0.047].
CONCLUSIONS: EGFR amplification is not an independent prognosis factor for PFS in advanced non-squamous NSCLC patients receiving first-line TKIs. However, it is an independent risk factor for PFS in the brain metastasis population.
摘要：
背景：表皮生长因子受体（EGFR）扩增是指EGFR基因的拷贝数增加，通常被认为是表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）耐药的“旁路”途径。我们旨在探讨EGFR扩增对EGFR突变治疗初治晚期非鳞状非小细胞肺癌（NSCLC）患者的影响。
方法：我们在单中心进行了一项前瞻性观察研究，在2019年3月3日至2022年2月1日期间招募接受酪氨酸激酶抑制剂（TKIs）的晚期非鳞状NSCLC患者。下一代测序（NGS）用于检测肿瘤组织样品中的遗传改变。使用Kaplan-Meier方法进行无进展生存(PFS)曲线。单因素和多因素分析用于评估影响TKIs疗效的因素。
结果：在这项研究中确定了总共117名未经治疗的晚期NSCLC患者。117例EGFR突变患者中有22例(18.8%)存在EGFR扩增。22例EGFR扩增患者中，10例患者携带EGFR19del，11例21-L858R。中位随访时间为22.47个月。有无EGFR扩增的患者的中位PFS分别为8.25个月和10.67个月。分别(对数秩检验，P=0.63）。在多变量分析中，EGFR扩增并不是一线TKI患者的独立预后因素[HR=1.38,95CI(0.73-2.58),P=0.321]。亚组分析显示，EGFR扩增是脑转移人群进展的危险因素。[HR=2.28，95CI（1.01，5.14），P=0.047]。
结论：EGFR扩增不是接受一线TKIs的晚期非鳞状细胞肺癌患者PFS的独立预后因素。然而,是脑转移人群PFS的独立危险因素。
方法：我们在单中心进行了一项前瞻性观察研究，在2019年3月3日至2022年2月1日期间招募接受酪氨酸激酶抑制剂（TKIs）的晚期非鳞状NSCLC患者。下一代测序（NGS）用于检测肿瘤组织样品中的遗传改变。使用Kaplan-Meier方法进行无进展生存(PFS)曲线。单因素和多因素分析用于评估影响TKIs疗效的因素。
结果：在这项研究中确定了总共117名未经治疗的晚期NSCLC患者。117例EGFR突变患者中有22例(18.8%)存在EGFR扩增。22例EGFR扩增患者中，10例患者携带EGFR19del，11例21-L858R。中位随访时间为22.47个月。有无EGFR扩增的患者的中位PFS分别为8.25个月和10.67个月。分别(对数秩检验，P=0.63）。在多变量分析中，EGFR扩增并不是一线TKI患者的独立预后因素[HR=1.38,95CI(0.73-2.58),P=0.321]。亚组分析显示，EGFR扩增是脑转移人群进展的危险因素。[HR=2.28，95CI（1.01，5.14），P=0.047]。
结论：EGFR扩增不是接受一线TKIs的晚期非鳞状细胞肺癌患者PFS的独立预后因素。然而,是脑转移人群PFS的独立危险因素。
