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EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation

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초록

The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

Abstract

The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

참고문헌 (4)

  1. Sequist LV, "Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors", Sci Transl Med, 3, pp.75ra26~ (2011)
  2. Ahn MJ, "Lazertinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer : results from the dose escalation and dose expansion parts of a first-in-human, open-label, multicentre, phase 1-2 study", Lancet Oncol, 20, pp.1681~1690 (2019)
  3. Shin HT, "Prevalence and detection of low-allele-fraction variants in clinical cancer samples", Nat Commun, 8, pp.1377~ (2017)
  4. Oxnard GR, "Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib", JAMA Oncol, 4, pp.1527~1534 (2018)

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