Clinical Outcomes of Different Generation <scp>EGFR TKIs</scp> in Susceptible <scp>EGFR</scp> ‐Mutated Advanced Nonsmall‐Cell Lung Cancer

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are indicated for advanced lung adenocarcinoma patients harboring susceptible EGFR mutations. The aim of this retrospective study was to compare the effectiveness of different generations of EGFR TKIs. We enrolled 421 patients with stage IV lung adenocarcinoma and sensitizing EGFR mutations receiving an EGFR-TKI as their first-line therapy, including first-generation (1st G, gefitinib and erlotinib), second-generation (2nd G, afatinib), and third-generation (3rd G, osimertinib) EGFR TKIs. The median progression free survival (PFS) (12.10 vs. 16.67 months vs. not reached; p = 0.0002) and overall survival (OS) (31.23 vs. 45.97 months vs. not reached; p = 0.0215) were significantly different between different generations of EGFR TKIs. 3rd G EGFR TKI provided the best PFS, particularly in patients with exon 19 deletion. The patients receiving 1st G EGFR TKIs (p = 0.005), with exon 19 deletion (p = 0.001) and PFS ≥ 270 days (p = 0.012) had a significantly higher T790M mutation rate. There was no survival difference between the patients receiving frontline 3rd G EGFR TKI and those receiving 3rd G EGFR TKI as sequential therapy (median OS 46.60 months vs. not reached, p = 0.1941). The OS of the patients who did not receive 3rd G EGFR TKI as sequential therapy was significantly worse than those receiving 3rd G EGFR TKI as first-line therapy (median OS 22.47 months vs. not reached, p = 0.0042). In conclusion, 3rd G EGFR TKI may provide better survival benefits as first-line therapy for patients harboring sensitizing EGFR mutations, particularly those with exon 19 deletion.