Next-Generation Sequencing at Initial NSCLC Workup May Improve Survival

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Non–small-cell lung cancer (NSCLC) has seen great advances in treatment due to the identification of oncogenic driver mutations and targeted treatment directed at these mutations.1 This has improved survival for patients with lung cancer, even in those with advanced disease.1 Current guidelines recommend biomarker testing for patients with NSCLC, but under-testing for these markers is widely reported.1 Economic factors, accessibility to testing, and insufficient tumor sample all contribute to this problem.1 In patients with lung cancer, tissue biopsy involves invasive procedures and often results in insufficient tumor content for testing.1 Circulating tumor DNA from cell-free DNA (cfDNA) released from tumor cell necrosis and apoptosis can be obtained in plasma samples to provide material for analysis by next-generation sequencing (NGS).1 However, NGS of plasma cfDNA is not standardized nor is it currently recommended by various oncology associations because of insufficient validity.1

Ongoing research studies are being conducted to validate the use of cfDNA NGS in NSCLC, including a recent study discussed at the European Lung Cancer Congress by Dr Chingyao Yang, who presented the results of a prospective observation study on the impact of cfDNA NGS on patients with advanced NSCLC who had no previous treatment. The study enrolled 180 treatment-naïve patients with suspected advanced NSCLC who received liquid NGS testing at the first visit. They were then randomized into 2 cohorts, with 87 patients in cohort A who received NGS results after molecular testing and pathological diagnosis and 93 patients in cohort B who received NGS results after the analysis was completed. Time to treatment was the primary end point. After excluding for early-stage NSCLC, small-cell lung cancer, benign diseases, and other types of cancer, cohort A consisted of 63 patients and cohort B consisted of 59 patients. Adenocarcinoma was the most common cancer type: 77.8% of group A and 79.7% of group B. EGFR mutation was found in 57.1% of group A and 56.6% of group B. Group A had 2 patients with ALK mutation and 1 patient with ROS1 mutation. Group B had 2 patients with BRAF mutation and 1 patient with MET exon 14 skipping mutation.

When time to treatment was analyzed, the median was 33 days for group A and 20 days for group B. Analysis of patients with EGFR mutation treated with an EGFR tyrosine kinase inhibitor found there was no difference in overall response rate or progression-free survival (PFS) between the 2 groups, but in patients treated with immunotherapy with or without chemotherapy, PFS in group B was longer than the PFS seen in group A. Liquid NGS earlier in the workup with patients with advanced NSCLC may improve survival.


  1. Fernandes MGO, Cruz-Martins N, Souto Moura C, et al. Clinical application of next-generation sequencing of plasma cell-free DNA for genotyping untreated advanced non-small cell lung cancer. Cancers (Basel). 2021;13(11):2707.

Source: Yang C, Shih J-Y, Liao W-Y, et al. The impact of liquid next-generation testing timing on treatment-naïve advanced non-small cell lung cancer: a prospective observational study. Ann Oncol. 2022;33(2):S58.

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