Liquid Biopsy Identifies EGFR-TKI Resistance Heterogeneity in Lung Cancer

Lung Cancer Advisor – by Andrea S. Blevins Primeau – 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.
• The C797S mutation was detected only among patients who received AZD9291.