Differential Responses to Targeted Therapies in Non-Small Cell Lung Cancer: A Comparative Analysis of Outcomes in Patients with Single EGFR Mutation and Concurrent Gene Alterations.

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 109 patients with EGFR mutations, 72 showed partial responses (66.1%), one had a complete response (0.9%), and 17 had stable disease (15.6%); 19 experienced progressive disease (17.4%). The overall response rate (ORR) was 67%, and the disease control rate (DCR) was 82.6%. Progression-free survival (PFS) was 15.03 months (95% CI: 13.17-16.89) in the single EGFR mutation group and 11.00 months (95% CI: 9.95-12.05) in the concurrent mutations group (P = 0.001). Among 43 patients with concurrent mutations, those with ALK mutations had the longest PFS (13.43 months), followed by PIK3CA (11.00 months), while MET alterations showed the shortest PFS (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.