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.
- 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).