WCLC 2025 - Posters & ePosters-EP.12.09 Third-Generation EGFR-TKIs in T790M-Negative NSCLC After First/Second-Generation EGFR-TKI Failure: A Retrospective Study

EP.12.09 Third-Generation EGFR-TKIs in T790M-Negative NSCLC After First/Second-Generation EGFR-TKI Failure: A Retrospective Study

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Pdf Summary

This retrospective study evaluated the efficacy of third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy and/or first- or second-generation EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations but lacking the T790M resistance mutation after failure of initial first- or second-generation EGFR-TKI therapy. The study enrolled 82 patients with exon 19 deletion or L858R EGFR mutations who progressed without acquiring T790M mutation.<br /><br />Results showed that treatment with third-generation EGFR-TKIs significantly improved median progression-free survival (PFS) to 10.2 months compared to 5.7 months in the group receiving non-third-generation treatments, including chemotherapy and earlier-generation EGFR-TKIs. The hazard ratio for PFS favored third-generation EGFR-TKIs (HR 0.54; 95% CI: 0.32–0.89; p=0.017). Overall survival (OS) was also longer in the third-generation EGFR-TKI group (median OS 39.8 vs. 32.4 months), although this difference was less pronounced.<br /><br />Subgroup analyses indicated no significant PFS difference between third-generation EGFR-TKIs and chemotherapy (10.2 vs. 6.8 months; p=0.727). However, third-generation EGFR-TKIs significantly outperformed first/second-generation EGFR-TKIs, both when combined with chemotherapy and when given alone, in terms of PFS.<br /><br />In conclusion, third-generation EGFR-TKIs provide a meaningful PFS benefit in T790M-negative EGFR-mutated advanced NSCLC patients after failure of first-line first- or second-generation EGFR-TKI therapy. These findings suggest that third-generation EGFR-TKIs represent a valuable treatment option beyond the current standard chemotherapy for this population.

Asset Subtitle

Xiaobi Huang

Meta Tag

Speaker Xiaobi Huang

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

third-generation EGFR-TKIs

non-small cell lung cancer

NSCLC

EGFR mutations

T790M-negative

exon 19 deletion

L858R mutation

progression-free survival

chemotherapy

first- and second-generation EGFR-TKIs