WCLC 2025 - Posters & ePosters-P2.02.42 Effect of MTHFR Gene Mutation on the Efficacy of Tyrosine Kinase Inhibitor Treatment in Lung Cancer Patients

P2.02.42 Effect of MTHFR Gene Mutation on the Efficacy of Tyrosine Kinase Inhibitor Treatment in Lung Cancer Patients

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This retrospective study at Guangdong Medical University investigated the impact of MTHFR gene mutations on the efficacy of EGFR-targeted tyrosine kinase inhibitors (TKIs) in treating advanced non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. Among 64 NSCLC patients receiving first-line EGFR-TKI therapy, 31.3% exhibited concurrent MTHFR mutations. The cohort was predominantly older than 60 years, predominantly female, mostly non-smokers, and primarily diagnosed with adenocarcinoma at advanced stages (III/IV).<br /><br />Next-generation sequencing identified EGFR exon 19 and 21 mutations, known drivers of NSCLC. Patients with MTHFR mutations treated with EGFR-TKIs demonstrated significantly longer progression-free survival (PFS) with a median of 28.5 months compared to 11.3 months in patients without MTHFR mutations (p=0.006). Multivariate analysis confirmed that age, EGFR mutation subtype, and presence of MTHFR mutation independently correlated with improved PFS, with MTHFR mutation carriers showing a 58% reduction in risk of progression (HR=0.419). However, overall survival (OS) did not significantly differ between MTHFR mutation-positive and -negative groups.<br /><br />The study highlights MTHFR as a common co-mutation in EGFR-mutated NSCLC and suggests that its presence enhances responsiveness to EGFR-TKIs, serving as a predictive biomarker for first-line targeted therapy efficacy. While MTHFR mutation improves PFS outcomes, it is not an independent prognostic factor for OS. These findings advocate for integrating MTHFR gene status into personalized treatment planning in advanced NSCLC, potentially improving therapeutic strategies and patient survival through tailored approaches. Further research is necessary to elucidate the underlying molecular mechanisms of enhanced drug sensitivity conferred by MTHFR mutations and to validate these clinical implications.

Asset Subtitle

Wenmei Su

Meta Tag

Speaker Wenmei Su

Topic Tumor Biology – Preclinical Biology

Keywords

MTHFR gene mutation

EGFR-targeted tyrosine kinase inhibitors

non-small cell lung cancer

EGFR mutations

progression-free survival

adenocarcinoma

next-generation sequencing

first-line therapy

personalized treatment

biomarker