应用新一代测序预测接受表皮生长因子受体酪氨酸激酶抑制剂治疗的晚期egfr突变肺腺癌患者的短期无进展生存期

IF 2.2 4区 医学 Q3 ONCOLOGY
Po-Hsin Lee, Yi-Chun Hsiao, Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Ho Lin, Gee-Chen Chang, Tsung-Ying Yang
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引用次数: 0

摘要

对于晚期egfr突变型肺腺癌患者,表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)药物可显著改善无进展生存期(PFS)。然而,一部分患者仍会经历早期疾病进展。在这项研究中,我们旨在通过下一代测序(NGS)分析确定与PFS缩短相关的潜在危险因素。这项回顾性研究纳入了接受一线EGFR-TKI治疗和前期NGS治疗的晚期egfr突变肺腺癌患者。遗传变异包括突变和拷贝数变异两种类型。涉及EGFR下游信号通路的改变被归类为“PIK3CA-AKT/RAS-RAF改变”。收集和分析临床和组织病理学资料。我们共研究了82例具有敏感EGFR突变的晚期肺癌患者。多变量分析显示,以下因素与PFS缩短相关:PIK3CA-AKT/RAS-RAF改变[风险比(HR) 3.197, P = 0.006]、年龄≤50 (HR 3.034, P = 0.010)、PD-L1≥50% (HR 2.256, P = 0.035)。根据上述危险因素将患者分为无危险组和≥1危险组。在无风险组中,与第一代/第二代EGFR-TKIs相比,第三代EGFR-TKIs的PFS数值更长(未达到vs. 20.0个月,P = 0.084)。然而,在危险因素≥1的患者中,第三代EGFR-TKIs没有PFS优势(6.6个月vs 6.2个月,P = 0.831)。总之,除了临床病理因素外,NGS为预测EGFR-TKI治疗后更短的PFS提供了额外的见解。我们确定了三个危险因素:(1)PIK3CA-AKT/RAS-RAF改变,(2)年龄≤50岁,(3)PD-L1≥50%。无论EGFR-TKI是否产生,具有这些因素的患者PFS都较差。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Applying next-generation sequencing to predict short progression-free survival in patients with advanced EGFR-mutant lung adenocarcinoma receiving epidermal growth factor receptor tyrosine kinase inhibitors.

For patients with advanced EGFR-mutant lung adenocarcinoma, progression-free survival (PFS) is significantly improved by epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) medications. However, a subset of patients still experiences early disease progression. In this study, we aimed to identify potential risk factors associated with shorter PFS through next-generation sequencing (NGS) analysis. This retrospective study included patients with advanced EGFR-mutant lung adenocarcinoma who received first-line EGFR-TKI treatment with upfront NGS. The genetic alterations included two types, mutations and copy number variations. Alterations involving EGFR downstream signaling pathways were classified as 'PIK3CA-AKT/RAS-RAF alterations'. Clinical and histopathological data were also collected and analyzed. We studied a total of 82 advanced lung cancer patients with sensitive EGFR mutations. Multivariable analyses showed associations with a shorter PFS for the following factors: PIK3CA-AKT/RAS-RAF alterations [hazard ratio (HR) 3.197, P = 0.006], age ≤50 (HR 3.034, P = 0.010), and PD-L1 ≥50% (HR 2.256, P = 0.035). Based on the above risk factors, patients were classified into no-risk and ≥1 risk groups. In the no-risk group, third-generation EGFR-TKIs showed a numerically longer PFS compared to first/second-generation EGFR-TKIs (not reached vs. 20.0 months, P = 0.084). However, in patients with ≥1 risk factor, third-generation EGFR-TKIs showed no PFS advantages (6.6 vs. 6.2 months, P = 0.831). In conclusion, besides clinicopathological factors, NGS provides additional insights to predict shorter PFS after EGFR-TKI treatment. We identified three risk factors: (1) PIK3CA-AKT/RAS-RAF alterations, (2) age ≤50, and (3) PD-L1 ≥50%. Patients with these factors had poor PFS regardless of EGFR-TKI generation.

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来源期刊
Anti-Cancer Drugs
Anti-Cancer Drugs 医学-药学
CiteScore
3.80
自引率
0.00%
发文量
244
审稿时长
3 months
期刊介绍: Anti-Cancer Drugs reports both clinical and experimental results related to anti-cancer drugs, and welcomes contributions on anti-cancer drug design, drug delivery, pharmacology, hormonal and biological modalities and chemotherapy evaluation. An internationally refereed journal devoted to the fast publication of innovative investigations on therapeutic agents against cancer, Anti-Cancer Drugs aims to stimulate and report research on both toxic and non-toxic anti-cancer agents. Consequently, the scope on the journal will cover both conventional cytotoxic chemotherapy and hormonal or biological response modalities such as interleukins and immunotherapy. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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