Third-Generation EGFR-TKIs Combined With Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Real-World Study

FLAURA2 has demonstrated that third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) plus chemotherapy brought a significant survival benefit over EGFR-TKI monotherapy. This suggests that EGFR-TKIs combined with chemotherapy may be a viable therapeutic strategy. Our study aimed to evaluate the efficacy, safety, and progression pattern of third-generation EGFR-TKIs combined with chemotherapy in advanced EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC) in the real world. This study designed as an observational, retrospective, single-center, real-world project enrolled 382 NSCLC individuals receiving third-generation EGFR-TKIs combined with platinum-based chemotherapy as first-line therapy. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). From July 2016 to May 2024, 382 patients were retrospectively included for the analysis. Of these patients, 120, 165, and 97 patients received osimertinib, aumolertinib, and furmonertinib plus chemotherapy as first-line therapy, respectively. Overall, the median follow-up duration was 34.6 months (95% CI: 32.2-35.6), the median PFS was 30.9 months (95% CI: 27.5-39.3), and the median OS was 53.9 months (95% CI: 46.2-NR). Overall, the ORR was 76.4% and the DCR was 98.2%. One hundred thirty-seven (35.9%) individuals experienced Grade 3 or higher AEs. Different third-generation EGFR-TKI groups show no statistically significant difference in PFS (HR = 0.75; 95% CI: 0.51-1.10; p = 0.25) after inverse probability of treatment weighting (IPTW), nor in AEs or severe AEs (p = 0.852; p = 0.502). First-line third-generation EGFR-TKI combined with pemetrexed-based chemotherapy demonstrated a favorable ORR and PFS benefit in advanced EGFRm NSCLC.