Introduction: Next‐generation sequencing (NGS) of cell‐free circulating tumor DNA (cfDNA) enables noninvasive genomic analysis of NSCLC patients. Although plasma‐detected genomic alterations (GAs) have been shown to predict targeted therapy response, evidence of durability of response is lacking or limited to small cohorts as is the impact of cfDNA NGS results on clinical decisions. Methods: This retrospective study of stage IIIB/IV NSCLC patients between the years 2014 and 2017 in Israel used cfDNA NGS (Guardant360; Guardant Health, Inc., Redwood City, California) to identify targetable GAs. Results: We consecutively tested 116 NSCLC patients, 41.4% before first‐line therapy (group A), 34.5% upon progression on chemotherapy or immunotherapy (group B1), and 24.1% upon progression on EGFR tyrosine kinase inhibitors (group B2). Targetable GAs were found in 31% of group A (15 of 48 patients), 32.5% in group B1 (13 of 40 patients) and 71% in group B2 (20 of 28 patients). Treatment decision was changed to targeted therapy in 23% (11 of 48 patients), 25% (10 of 40 patients) and 32% (9 of 28 patients), respectively (total cohort 26%; 30/116). Objective response rate (Response Evaluation Criteria in Solid Tumors) was 43% (12 of 28 patients) including one complete response, partial response in 39% (11 of 28 patients), stable disease in 32% (9 of 28 patients), and progressive disease in 25% (7 of 28 patients). Disease control rate was 75% for 5 months median treatment duration. Conclusions: Comprehensive cfDNA testing impacted clinical decisions in one‐quarter to one‐third of initial and subsequent lines of treatment in advanced NSCLC patients. This retrospective study extends previous reports by showing that responses based on cfDNA are durable and change treatment decisions at initial presentation and at progression.

中文翻译：

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循环游离 DNA 综合基因组检测对晚期肺癌的临床影响

简介：无细胞循环肿瘤 DNA (cfDNA) 的下一代测序 (NGS) 能够对 NSCLC 患者进行无创基因组分析。尽管血浆检测到的基因组改变 (GA) 已被证明可以预测靶向治疗反应，但缺乏反应持久性的证据或仅限于小队列，因为 cfDNA NGS 结果对临床决策的影响也是如此。方法：这项对 2014 年至 2017 年间在以色列进行的 IIIB/IV 期 NSCLC 患者的回顾性研究使用 cfDNA NGS（Guardant360；Guardant Health, Inc.，Redwood City, California）来识别可靶向的 GA。结果：我们连续检测了 116 名 NSCLC 患者，一线治疗前为 41.4%（A 组），化疗或免疫治疗进展后为 34.5%（B1 组），EGFR 酪氨酸激酶抑制剂治疗后进展为 24.1%（B2 组）。在 A 组中 31%（48 名患者中的 15 名）、B1 组（40 名患者中的 13 名）和 B2 组（28 名患者中的 20 名）中发现了 32.5% 的可靶向 GA。分别有 23%（48 名患者中的 11 名）、25%（40 名患者中的 10 名）和 32%（28 名患者中的 9 名）（总队列 26%；30/116）将治疗决定改为靶向治疗。客观缓解率（实体瘤中的缓解评估标准）为 43%（28 名患者中的 12 名），包括 1 名完全缓解，39%（28 名患者中的 11 名）部分缓解，32%（28 名患者中的 9 名）病情稳定，以及25% 的疾病进展（28 名患者中的 7 名）。中位治疗时间为 5 个月，疾病控制率为 75%。结论：综合 cfDNA 检测影响了晚期 NSCLC 患者初始和后续治疗线的四分之一到三分之一的临床决策。