Author of

• 36336

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  P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Targeted Therapy - Clinically Focused
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 36362

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    P76.22 - Acquired an EGFR Amplification in EGFR Exon 20 insertion Lung Adenocarcinoma Resistant to First Line Osimertinib Treatment (ID 1316)

    00:00 - 00:00  |  Presenting Author(s): Chengwei Zhou
    • Abstract
    • Slides

    Introduction
    

    Osimertinib, a new third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been demonstrated promising antitumor activity in certain EGFR Exon 20 insertion (EGFRex20ins) mutant patients with advanced non-small-cell lung cancer (NSCLC). However, resistance to osimertinib inevitably occurs after approximately a few months treatment, the mechanisms of acquired resistance to first-line osimertinib treatment in patients harboring EGFR insertion mutations, which accounts for approximately 4-10% of EGFR mutations, remain unclear.

    Methods
    

    Mutation and copy number variation analysis by next-generation sequencing (NGS) were performed on pre-treatment pleural effusion and post-progression clavicular lymph nodes. Radiological follow-up was performed at the first month then once every 2 months with computed tomography (CT) of the thorax and upper abdomen. Response was assessed according to Response Criteria in Solid Tumors (RECIST) 1.1. Progression-free survival (PFS) was defined as the interval from the date of initiation of osimertinib therapy to the date of disease progression.

    Results
    

    We present a 29-year-old female nonsmoking patient diagnosed with metastatic lung adenocarcinoma involving the right lung. Genetic testing of the pleural effusion by NGS of more than 800 cancer-related genes showed the presence of an EGFRex20ins (p.M766delinsMASV,17.21%) along with a frameshift truncating deletion mutation of TP53 (exon9 p.K319fs,13.20%). She was negative for oncogenic alterations in KRAS, anaplastic lymphoma kinase(ALK), ROS1, met proto-oncogene (MET), and ret protooncogene (RET). The patient received first-ine osimertinib (80mg once daily) treatment and achieved a progression-free survival (PFS) of 7.2 months and continues on the dose of osimertinib after having progressed disease. Analysis of the post-progression biopsy of the patient with a partial response (PR) after osimertinib treatment revealed an EGFR amplification (CNV, 4.569), a known resistance mechanism to EGFR TKIs. Currently, the patient is doing well without any side effects and continues on osimertinib.

    Conclusion
    

    This is the first case report of an EGFRex20ins patient who developed resistance to osimertinib as a result of acquired an EGFR amplification, which provides valuable information for the discovery of resistance mechanisms to osimertinib and guidance for personalized NSCLC treatment in such patients. The finding of the present case suggests that acquired EGFR amplification can occur even when the patient harbors an EGFR insertion mutation after EGFR-tyrosine kinase inhibitor treatment. Incorporating EGFR inhibitors into the treatment regimens of patients acquiring EGFR amplification merits additional study.

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