联合分析循环肿瘤 DNA 和肿瘤组织以克服奥希替尼耐药性（OSIRIS）；二线奥希替尼队列

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2024-09-28 DOI:10.1016/j.lungcan.2024.107972

J.W.T. van der Wel , M. Jebbink , D. van den Broek , L.C. Steinbusch , W.S.M.E. Theelen , G. Ruiter , W. Buikhuisen , J.A. Burgers , P. Baas , M. Vermeulen , V. van der Noort , S.M.S. Hashemi , L.J.W. Bosch , K. Monkhorst , E.F. Smit , M.C. Boelens , A.J. de Langen

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引用次数: 0

摘要

导言表皮生长因子受体（EGFR）突变的 NSCLC 不可避免地会出现奥希替尼耐药性。我们的目的是利用二线/三线奥希替尼治疗进展患者的配对血浆和肿瘤样本确定耐药机制（RM）。血浆测序使用 AVENIO Expanded Panel（仅供研究使用），肿瘤活检进行 DNA 和 RNA 测序以及组织学评估。当驱动基因突变得到确认且变异等位基因频率≥0.10%时，测序即为成功。针对两种模式中的驱动基因突变和RMs，计算模式间的一致性。结果42/51份血浆样本（82%）和50/51份肿瘤样本（98%）检测到驱动基因突变，一致率为80%。在 41/51 例（80%）患者中，发现了≥1 个 RM。在血浆（61.5%）中发现了 32 个两种模式都涵盖的 RM，在肿瘤（75%）中发现了 39 个，在两种模式中都发现了 19 个。结论无论采用哪种比较方法，对奥希替尼二线/三线治疗后的血浆和肿瘤样本进行联合分析都能发现更多的RM。血浆测序鉴定出61.5%的RM，肿瘤分析鉴定出75%的RM。两者结合可提供奥希替尼耐药的更佳概况，从而提供更有针对性的治疗方案。

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Combined analysis of circulating tumor DNA and tumor tissue to overcome osimertinib resistance (OSIRIS); the second line osimertinib cohort

Introduction

Osimertinib resistance inevitably occurs in EGFR mutated NSCLC. We aimed to identify resistance mechanisms (RM) using paired plasma and tumor samples in patients that progressed on 2nd/3rd line osimertinib.

Methods

From 09 – 2019 to 02 – 2021, 51 patients were enrolled. Plasma sequencing used AVENIO Expanded Panel (research use only), tumor biopsies underwent DNA and RNA sequencing and histological evaluation. Sequencing was regarded successful when the driver mutation was confirmed with a variant allele frequency of ≥0.10%. Concordance between modalities was calculated for the driver mutation and RMs covered in both modalities. The Molecular Tumor Board formulated a treatment advice.

Results

The driver mutation was detected in 42/51 plasma samples (82%) and in 50/51 tumor samples (98%), concordance rate was 80%. In 41/51 (80%) patients ≥1 RM was identified. Thirty-two RMs covered in both modalities were found in plasma (61.5%), 39 in tumor (75%), nineteen in both. RM concordance rate was 36.5%.

Conclusion

Combined analysis of plasma and tumor samples post 2nd/3rd line osimertinib identifies additional RMs regardless of the comparative approach used. Plasma sequencing identified 61.5% of RMs, tumor analysis identified 75%. Combined, they provide a superior overview of osimertinib resistance, enabling more tailored treatment options.

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.