# Clinical Outcomes of Different Generation EGFR TKIs in Susceptible EGFR‐Mutated Advanced Nonsmall‐Cell Lung Cancer

## TL;DR

This study compares the effectiveness of different generations of EGFR inhibitors in treating advanced lung cancer and finds that third-generation drugs offer the best outcomes.

## Contribution

The study provides new evidence that third-generation EGFR TKIs are more effective as first-line therapy for specific EGFR mutations.

## Key findings

- Third-generation EGFR TKIs provided the best progression-free survival, especially in patients with exon 19 deletion.
- Patients receiving first-generation EGFR TKIs had a higher T790M mutation rate.
- Using third-generation EGFR TKIs as first-line therapy significantly improved overall survival compared to not using them.

## Abstract

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.