2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-EP02.11

EP02.11 - Jiao Yang

Pdf Summary

The document investigates the treatment responses and resistance mechanisms in non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping mutations (METex14). This mutation is present in about 1-3% of NSCLC cases and poses significant therapeutic challenges. The study focuses on two MET tyrosine kinase inhibitors (TKIs): crizotinib and vebreltinib.<br /><br />The clinical trial observed 12 patients with METex14-mutated NSCLC, analyzing treatment effectiveness and resistance mechanisms. Results showed that crizotinib had a mean progression-free survival (PFS) of 4.4 months, whereas vebreltinib exhibited a significantly longer mean PFS of 16.9 months. Notably, all patients treated with vebreltinib achieved a PFS of more than 7.3 months, as opposed to the five out of eight patients treated with crizotinib who had a PFS of less than 3.0 months.<br /><br />Resistance mechanisms identified included secondary MET mutations like D1228N and EGFR amplification. Additionally, one patient displayed pulmonary sarcomatoid carcinoma (PSC) transformation post-MET-targeted therapy failure. The study noted that after MET TKI treatment failure, patients with high PD-L1 expression could potentially benefit from a combined regimen of camrelizumab and endostar, achieving a 13.0-month PFS in one case.<br /><br />The research highlights vebreltinib's superiority in treating METex14 NSCLC and suggests that patient-derived organoids (PDOs) could effectively predict treatment responses. The findings suggest that integrating immunotherapy with anti-angiogenic treatment may be advantageous for NSCLC patients with high PD-L1. The study emphasizes the need for further exploration of alternative therapeutic strategies post-MET TKI treatment failure, especially considering the possibility of pathological transformations like PSC.

Keywords

non-small cell lung cancer

NSCLC

MET exon 14 skipping mutations

METex14

crizotinib

vebreltinib

resistance mechanisms

progression-free survival

PD-L1 expression

immunotherapy