Comparative Efficacy of First-Line versus Further-Line Icotinib Therapy in Advanced Lung Adenocarcinoma: A Real-World Cohort Study

Abstract

Background The optimal sequencing of EGFR tyrosine kinase inhibitors (TKIs) in advanced lung adenocarcinoma remains controversial. This study aimed to compare the efficacy of icotinib as first-line versus further-line therapy in a real-world setting. Methods A retrospective cohort study was conducted at Quzhou People’s Hospital involving 45 patients with advanced lung adenocarcinoma, including 40 with EGFR‑mutant (exon 19 deletions or L858R) and 5 with wild‑type EGFR, treated with icotinib between January 2020 and December 2024. Patients were stratified into first-line (n=25) and further-line (n=20) groups. Efficacy endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariate Cox regression analyses adjusted for potential confounders. Results The first-line group demonstrated significantly superior outcomes: ORR 80.0% vs. 30.0% (p=0.0005), median PFS 18.9 months vs. 13.1 months (Cox regression: HR 2.82, 95% CI: 1.18–6.95, p=0.0239), and median OS 51.2 months vs. 35.15 months (Cox regression: HR 3.05, 95% CI: 1.09–8.53, p=0.0339). Multivariate analysis confirmed treatment line as an independent predictor of PFS and OS. Poor ECOG PS (HR 2.65, p=0.0234) and metastatic organs ≥3 (HR 1.77, p=0.0457) were additional negative prognostic factors for OS. Conclusion Icotinib showed better efficacy as first-line therapy than as further-line therapy. However, considering the retrospective, single-center design and small sample size, the results should be interpreted with caution. Baseline clinical factors (ECOG PS and metastatic burden) remained critical for survival outcomes.