表皮生长因子受体（EGFR）-T790M突变非小细胞肺癌（NSCLC）患者对奥希替尼治疗获得性耐药的基因组变异分析。

IF 2.8 3区医学 Q2 ONCOLOGY Clinical & Translational Oncology Pub Date : 2024-09-24 DOI:10.1007/s12094-024-03727-7

Ping-Chih Hsu, John Wen-Cheng Chang, Li-Chung Chiu, Cheng-Ta Yang, Scott Chih-Hsi Kuo, Yueh-Fu Fang, Chiao-En Wu

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引用次数: 0

摘要

背景和目的：晚期T790M突变非小细胞肺癌（NSCLC）耐受奥希替尼治疗后发生的基因组改变非常复杂，人们对此知之甚少。在这项研究中，我们旨在通过对组织和液体活检组织进行全面的新一代测序（NGS）来检测这些基因组变化：从 2020 年 9 月到 2021 年 6 月，我们招募了 31 例 IIIB/IV 期 T790M 突变的 NSCLC 患者，这些患者在接受奥希替尼治疗后病情出现进展，并提供了书面知情同意书。分别从 31 名和 18 名患者中采集了用于 NGS 检测的液体和组织活检样本。18名研究患者的组织活检和液体活检的NGS数据成对：关于 T790M 突变状态，液体和组织活检样本的保留率和丢失率分别为 33% 和 67%。5名患者（16.1%）存在C797S突变（4份液体样本和1份组织样本）。2人（6.5%）有MET突变，3人（9.7%）有BRAF-V600E突变，1人（3.2%）有KRAS-G12C突变。在接受组织活检的18名患者中，保留T790M突变的患者接受奥希替尼治疗后的无进展生存期（PFS）明显长于T790M突变缺失的患者（10.8个月 vs. 5.0个月，P = 0.045）。在所有患者中，与根据液体活检结果保留T790M突变的患者相比，液体活检样本中T790M突变缺失的患者接受奥希替尼治疗后的PFS（10.8个月 vs. 7.5个月，P = 0.209）和进展后生存期（17.7个月 vs. 9.6个月，P = 0.132）更长：结论：使用组织或液体活检样本对奥希替尼治疗获得性耐药的晚期T790M突变NSCLC患者进行NGS检测，可以发现各种基因组变异。未来的研究有必要以 NGS 结果为基础，重点研究后续的定制疗法。

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Analysis of genomic alternations in epidermal growth factor receptor (EGFR)-T790M-mutated non-small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib therapy.

Background and objectives: Genomic alterations after resistance to osimertinib therapy in advanced T790M-mutated non-small cell lung cancer (NSCLC) are complex and poorly understood. In this study, we aimed to detect these genomic alternations via comprehensive next-generation sequencing (NGS) of tissue and liquid biopsies.

Patients and methods: From September 2020 to June 2021, 31 stage IIIB/IV T790M-mutated NSCLC patients who exhibited progressive disease after osimertinib therapy and provided written informed consent were recruited. Liquid and tissue biopsy samples for NGS testing were collected from 31 and 18 patients, respectively. Eighteen study patients had paired NGS data from tissue and liquid biopsies.

Results: With respect to the T790M mutation status, the preservation and loss rates were 33% and 67%, respectively, in both liquid and tissue biopsy samples. Five patients (16.1%) had the C797S mutation (4 liquid samples and 1 tissue sample). Two (6.5%) had MET mutations, 3 (9.7%) had BRAF-V600E mutations, and 1 (3.2%) had a KRAS-G12C mutation. Among the 18 patients who underwent tissue rebiopsies, those with preserved T790M mutation had significantly longer progression-free survival (PFS) with osimertinib therapy than those with T790M mutation loss (10.8 vs. 5.0 months, P = 0.045). Among all patients, those with T790M mutation loss in liquid biopsy samples had longer PFS after osimertinib therapy (10.8 vs. 7.5 months, P = 0.209) and postprogression survival (17.7 vs. 9.6 months, P = 0.132) than those with preserved T790M mutation based on liquid biopsies.

Conclusions: NGS using either tissue or liquid biopsy samples from advanced T790M-mutated NSCLC patients with acquired resistance to osimertinib therapy can detect various genomic alternations. Future studies focusing on subsequent tailored therapies on the basis of NGS results are warranted.

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来源期刊

Clinical & Translational Oncology 医学-肿瘤学

CiteScore

6.20

自引率

2.90%

发文量

240

审稿时长

1 months

期刊介绍： Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.