Liquid Biopsy Identifies EGFR-TKI Resistance Heterogeneity in Lung Cancer

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A liquid biopsy analysis shows inter- and intra-patient heterogeneity of EGFR resistance mutations among patients with lung adenocarcinoma who received EGFR-directed TKI therapy.
A liquid biopsy analysis shows inter- and intra-patient heterogeneity of EGFR resistance mutations among patients with lung adenocarcinoma who received EGFR-directed TKI therapy.

A liquid biopsy analysis shows inter- and intra-patient heterogeneity of EGFR resistance mutations among patients with lung adenocarcinoma who received EGFR-directed tyrosine kinase inhibitor (TKI) therapy, according to a study that will be presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.1

Most patients receiving EGFR-TKI therapy will develop resistance and progressive disease. The purpose of this study was to evaluate the role of circulating tumor DNA (ctDNA) — or “liquid biopsy” — to identify molecular changes that may confer EGFR-TKI resistance.

The study collected ctDNA from 254 patients with advanced lung adenocarcinoma and used next-generation sequencing to identify molecular mutations.

At least 1 ctDNA mutation was identified among 172 patients, with 2 median number of plasma somatic mutations. The primary locations of mutations were in the EGFR and TP53 genes, followed by ERBB2 and PIK3CA.

EGFR-TKI–sensitizing mutations were not detected among 138 (54.3%) of patients, though 59 patients harbored the T790M/C797S mutation and 16 had mutations in the PI3K/AKT/mTOR pathway.

Multiple simultaneous resistance mutations occurred in 22 patients, which included 13 patients without TKI-sensitizing mutations.

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The C797S mutation was detected only among patients who received AZD9291.

These data suggest that “ctDNA can be used as a ‘liquid biopsy' to facilitate the broad exploration of potential resistance mechanisms,” indicated the investigators.

Reference

  1. Chen R, Zhao J, Hu X, et al. Circulating tumor DNA profiling to reveal heterogeneity of EGFR-TKI resistance mechanisms in lung adenocarcinoma patients. J Clin Oncol. 2017;35(suppl; abstr 11527).

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