Liquid Biopsies Detect Unknown Driver Mutations in Advanced NSCLC

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ctDNA next generation sequencing of patient blood samples detected oncogenic drivers in 27 (36%) patients, including HER2 exon 20 insYVMA, BRAF L597Q, and MET exon14 mutations.
ctDNA next generation sequencing of patient blood samples detected oncogenic drivers in 27 (36%) patients, including HER2 exon 20 insYVMA, BRAF L597Q, and MET exon14 mutations.
The following article features coverage from the IASLC 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan. Click here to read more of Cancer Therapy Advisor's conference coverage.

Editor's note: this article was updated to fix a typo in the first line.

Using liquid biopsy to obtain circulating tumor DNA (ctDNA), researchers used next generation sequencing (NGS) to identify unknown drivers and resistance mechanisms in patients with advanced non–small cell lung cancer (NSCLC) and effectively matched them to appropriate therapy, according to research presented at the International Association for the Study of Lung Cancer (IASLC) 18th Annual World Conference on Lung Cancer (WCLC) in Yokohama, Japan.1

For this study, researchers enrolled 76 patients with advanced NSCLC who had unknown oncogenic drivers. ctDNA NGS of patient blood samples detected oncogenic drivers in 27 (36%) patients, including HER2 exon 20 insYVMA, BRAF L597Q, and MET exon14 mutations. Eleven (14%) patients were matched to clinical trials, and 10 evaluable patients had a partial response.

NGS detected plasma ctDNA in 46 (60%) patients, with detection rates of 46% and 73% when blood was drawn during active treatment compared with off-treatment draws, respectively (odds ratio [OR], 0.31; 95% CI, 0.12-0.81; P = .02).

Twenty-five concurrent tissue NGS tests were performed, which revealed a 96% plasma match with tissue and a 60% tissue match with plasma for oncogenic driver mutations.

The mean turnaround time for plasma NGS was 6 days compared with 21 days for tissue NGS (P < .0001).

The authors noted that plasma ctDNA is most detectable at metastatic disease diagnosis or at progression, and though positive findings of driver mutations are very specific and may drive treatment, a tissue biopsy may be required upon negative findings.

Read more of Cancer Therapy Advisor's coverage of the IASLC 18th World Conference on Lung Cancer (WCLC) by visiting the conference page.

Reference

  1. Sabari JK, Stephens D, Ni A, et al. Liquid biopsy in the lung cancer clinic: a prospective study of plasma DNA next generation sequencing to guide matched therapy. Presented at: International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer; Yokohama, Japan: October 15-18, 2017. Abstract OA 10.03.

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