2023 World Conference on Lung Cancer (Posters)-EP12.01. Autopsy and Next Generation Sequencing Report of First-Line Treatment with Osimertinib for EGFR-Mutated Squamous Cell Carcinoma of the Lung

EP12.01. Autopsy and Next Generation Sequencing Report of First-Line Treatment with Osimertinib for EGFR-Mutated Squamous Cell Carcinoma of the Lung - PDF(Slides)

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This report discusses the case of a patient with epidermal growth factor receptor (EGFR)-mutated squamous cell carcinoma (SCC) of the lung who was unresponsive to osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, as a first-line treatment. The effectiveness of osimertinib in EGFR-mutated lung SCC is unclear, and there are only a few reports on its use in this type of lung cancer. The autopsy findings confirmed the diagnosis of lung SCC, and a next-generation sequencing analysis revealed multiple genetic abnormalities, including TP53 mutation and amplification of CDK6 and KRAS, which have previously been associated with resistance to osimertinib. <br /><br />The case report suggests that next-generation sequencing can help explain why osimertinib is ineffective in EGFR-mutated SCC, and highlights the importance of analyzing coexisting genetic abnormalities in patients with EGFR mutant-positive SCC. The authors recommend considering therapy with an EGFR tyrosine kinase inhibitor if no additional gene associated with resistance to tyrosine kinase inhibitors is detected. The report provides a table of somatic gene amplifications detected by next-generation sequencing in the tumor tissue, including genes such as FGF10, CDK6, FGFR1, MYC, RET, FGF23, FGF6, and KRAS.<br /><br />The patient in this case was an 83-year-old male diagnosed with SCC of the lung. Molecular analysis revealed a positive result for EGFR exon19 deletion, and he was treated with osimertinib. However, after 18 days of therapy, he experienced dyspnea and a computed tomography scan showed enlarged lung cancer. The autopsy and next-generation sequencing analysis were performed to understand why osimertinib was ineffective as a first-line treatment. The autopsy findings confirmed the diagnosis of lung SCC, and the next-generation sequencing analysis identified genetic abnormalities, including TP53 mutation and amplification of CDK6 and KRAS, which may have contributed to the lack of response to osimertinib. The report concludes that these tumor cell-associated gene abnormalities may explain the ineffectiveness of osimertinib in this case.

Asset Subtitle

Tadashi Nishimura

Meta Tag

Speaker Tadashi Nishimura

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

epidermal growth factor receptor

EGFR-mutated squamous cell carcinoma

lung cancer

osimertinib

EGFR-tyrosine kinase inhibitor

next-generation sequencing

TP53 mutation

CDK6 amplification

KRAS amplification

tyrosine kinase inhibitors