2022 World Conference on Lung Cancer (ePosters)-EP08.02-150. Molecular Heterogeneity of Compound Epidermal Growth Factor Receptor (EGFR) Mutations in Lung Adenocarcinoma (LAC)

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This study examines the molecular heterogeneity of compound epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LAC). EGFR exon 19 deletions and exon 21 L858R point mutation are the most common EGFR gene mutations, accounting for nearly 90% of cases. Compound mutations occur when more than one EGFR mutation is present in the same tumor, and they are reported to occur in around 5% of LAC cases in the Caucasian population. The researchers reviewed the electronic health records of 17 patients diagnosed with LAC with compound EGFR mutations at a regional cancer center in the United Kingdom between 2014 and 2021. They analyzed the demographics, clinical, tumor, and molecular characteristics, as well as treatment outcomes of these patients.<br /><br />The results showed that out of the 17 patients, 4 were male and 13 were female, with a median age of 65 years. Six patients presented with brain metastases. Eleven patients had been treated with EGFR tyrosine kinase inhibitors (TKIs), either as first-line or third-line treatment. The most common TKIs used were afatinib, osimertinib, gefitinib, and erlotinib. The median overall survival for the TKI treated cohort was 8 months, ranging from 0.25 to 41 months.<br /><br />The distribution of EGFR mutations in the tumors varied, with 5 tumors having common mutations (exon 19 deletion or exon 21 L858R point mutation) and 12 having uncommon compound mutations. One patient had an additional exon 20 T790M mutation on subsequent biopsy. Additional mutations were also found in TP53, PTEN, SMAD4, and CTNNB. Eight tumors had extra copies of the ALK gene but no translocation.<br /><br />In conclusion, LAC with compound EGFR mutations is a heterogeneous group. Common mutations were less frequent than expected, with uncommon mutations involving EGFR exons 20 and 21 being more common. No common compound mutations were observed. The overall survival in this cohort treated with TKIs was shorter than expected for LAC patients with a single mutation. Overall, this study provides insight into the molecular profile and treatment outcomes of LAC with compound EGFR mutations.

Asset Subtitle

Ramesh Bulusu

Meta Tag

Speaker Ramesh Bulusu

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

molecular heterogeneity

compound EGFR mutations

lung adenocarcinoma

EGFR exon 19 deletions

exon 21 L858R point mutation

EGFR gene mutations

tumor

Caucasian population

electronic health records

regional cancer center