2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP01.57

PP01.57 - Mansi Sharma

Pdf Summary

This study investigates the differential sensitivities of epidermal growth factor receptor (EGFR) exon 19 deletion (ex19del) mutations to second and third-generation tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients. Conducted by researchers from various institutions in India, it utilizes next-generation sequencing (NGS) to analyze the clinical outcomes of 365 cases out of 850 EGFR mutated NSCLC patients. <br /><br />The main aim is to understand whether all exon 19 EGFR mutations demonstrate similar sensitivity to TKIs or exhibit different outcomes. The study categorizes ex19del mutations into two groups: C-helix and classical exon 19 deletions. Of the 310 patients who underwent NGS testing, 76 (24.5%) had C-helix mutations, while 234 (75.5%) exhibited classical exon 19 deletions. <br /><br />Results indicate that patients with C-helix ex19del mutations had a longer progression-free survival (PFS)—16.9 months compared to 11.5 months for classical mutations when treated with EGFR TKIs—though the statistical significance was marginal (p=0.04). Furthermore, the response rate to the second-generation TKI, Afatinib, was higher in C-helix patients (73%) as opposed to those treated with the third-generation TKI, Osimertinib (64%). Overall survival was also notably longer for the C-helix group (median 29.8 months vs. 22 months, p=0.05).<br /><br />The study highlights that detailed molecular characterization using NGS can influence therapeutic strategies and potentially improve patient outcomes differing from generic single-gene testing methods. The significantly higher rate of C-helix mutations observed in this cohort raises an interesting discussion on the potential need for broader-based NGS testing to capture these variations effectively. Further functional studies are recommended to enhance understanding of drug sensitivities associated with these mutations.

Keywords

EGFR

exon 19 deletion

tyrosine kinase inhibitors

non-small cell lung cancer

next-generation sequencing

C-helix mutations

classical exon 19 deletions

progression-free survival

Afatinib

Osimertinib