Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report.

Abstract

BACKGROUND:

Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib.

CASE REPORT:

We report the case of a 78-year-old non-smoker woman with stage IV EGFR L858R-positive lung adenocarcinoma presented with T790M mutation after five years of treatment with gefitinib. The patient was started on osimertinib, but after two and a half years of treatment experienced disease progression. The analyses of circulating tumor DNA using next-generation sequencing showed, together with the pre-existing T790M and exon 21 L858R, the presence of the EGFR C797G resistance mutation.

CONCLUSION:

Our case report revealed a rare EGFR-dependent acquired resistance mutation to osimertinib in circulating tumor DNA. Liquid biopsy appears to be a promising resource to understand the biology of osimertinib resistance by clonal evolution monitoring and the identification of novel resistance mechanisms.

• Authors: Elisa DE Carlo, Monica Schiappacassi, Giacomo Pelizzari, Tania Baresic, Alessandro Del Conte, Brigida Stanzione, Valentina DA Ros, Roberto Doliana, Gustavo Baldassarre, Alessandra Bearz
• Journal: In vivo (Athens, Greece) (In Vivo) 2021 Sep-Oct Vol. 35 Issue 5 Pg. 2941-2945 ISSN: 1791-7549 [Electronic] Greece
• PMID: 34410991 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Acrylamides
• Aniline Compounds
• Protein Kinase Inhibitors
• osimertinib
• EGFR protein, human
• ErbB Receptors

Topics

• Acrylamides
• Aged
• Aniline Compounds
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Drug Resistance, Neoplasm (genetics)
• ErbB Receptors (genetics)
• Female
• Humans
• Liquid Biopsy
• Lung Neoplasms (drug therapy, genetics)
• Mutation
• Protein Kinase Inhibitors (therapeutic use)