2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP02.15

PP02.15 - Nuruddin Mohammad Iqbal

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This preliminary study from India investigates the prevalence and characteristics of MET gene alterations in EGFR-mutant lung adenocarcinoma patients who have developed resistance to tyrosine kinase inhibitors (TKIs). A total of 100 tissue biopsies from post-TKI treatment were analyzed at the All India Institute of Medical Sciences, New Delhi. The median patient age was 51 years, with a near-equal gender distribution. The most common baseline EGFR mutations were exon 19 deletions and exon 21 L858R mutations.<br /><br />Patients were treated with EGFR TKIs, alone or combined with chemotherapy, with a median progression time of 10.5 months. Post-TKI analyses revealed that EGFR exon 20 T790M mutations were present in 32 patients, small cell transformations occurred in 13 patients, and one patient showed sarcomatoid transformation.<br /><br />FISH assay results highlighted that MET gene amplification was present in 18.5% of cases, detected in both smokers and non-smokers equally. Some cases exhibited co-occurrence of MET amplification with T790M mutations or small cell transformation, indicating MET alterations are not mutually exclusive with other resistance mechanisms. However, targeted Next Generation Sequencing (NGS) in a smaller subset found no MET gene mutations.<br /><br />The study underscores the critical role of MET alterations, especially gene amplifications, in acquired resistance to EGFR TKIs. The conclusions suggest that routine FISH analysis in post-TKI biopsies, alongside NGS, should be integrated into biomarker testing protocols to effectively identify these targetable alterations. This approach might guide personalized medicine strategies and optimize treatment regimens for patients with resistant EGFR-mutant lung adenocarcinoma. The findings align with global literature, reinforcing similar prevalence rates and supporting the potential for combined therapy strategies involving EGFR and MET inhibitors.

Keywords

MET gene alterations

EGFR-mutant lung adenocarcinoma

tyrosine kinase inhibitors resistance

All India Institute of Medical Sciences

EGFR mutations

MET amplification

FISH assay

Next Generation Sequencing

personalized medicine

biomarker testing