Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improve the quality of life in individuals with EGFR mutation-positive non-small cell lung cancer (NSCLC). This study evaluates the treatment outcomes of EGFR-mutant NSCLC patients with concurrent gene alterations, aiming to determine their predictive significance concerning responses to EGFR-TKI therapy. Materials and Methods We conducted a retrospective cohort study using next-generation sequencing (NGS) data from January 2019 to June 2023. Patients were categorized into two groups: those with a single EGFR mutation (Group 1) and those with concurrent EGFR mutations (Group 2). Results Among 121 patients with EGFR mutations, 80 (66.1%) achieved partial responses, three (2.5%) achieved complete responses, and 16 (13.2%) had stable disease, while 22 patients (18.2%) experienced progressive disease. The overall response rate (ORR) was 68.6%, and the disease control rate (DCR) was 81.8%. Median progression-free survival (PFS) was 15.09 months (95% CI, 13.57-18.21) in the single EGFR mutation group compared with 9.32 months (95% CI, 8.27-10.35) in the concurrent alteration group (P = 0.001). Consistently, overall survival (OS) was also longer in patients with single EGFR mutations (30.72 months) than in those with concurrent alterations (20.36 months). Among 57 patients harboring concurrent mutations, those with ALK alterations showed the longest PFS (13.44 months), followed by PIK3CA (9.48 months). In contrast, patients with KRAS and BRAF alterations had the poorest outcomes, with median PFS of 6.18 and 6.20 months, respectively, while MET alterations were associated with a PFS of 4.77 months. Conclusion Concurrent gene alterations in EGFR-mutant NSCLC are associated with reduced efficacy of EGFR-TKIs. Patients with KRAS, BRAF, ROS1, or MET mutations have poorer predictive outcomes compared to those without these alterations. This abstract is funded by: None
Le et al. (2026) studied this question.