@article{TLCR120026,
author = {Zipeng Wu and Tianyi Liu and Ruofan Yu and Jingwen Li and Shuyi Hu and Caolu Liu and Xinyu Du and Xinhong Shi and Yingying Dai and Lin Lu and Yuxin Ma and Yingying Jiang and Yue Shi and Guoren Zhou and Cheng Chen and Jiamin Shi and Ning Ding and Xiaohua Wang},
title = {Prognostic analysis and beneficiary population exploration of subsequent treatment regimens after third-generation EGFR-TKIs failure in EGFR-mutated advanced non-small cell lung cancer: a retrospective cohort study},
journal = {Translational Lung Cancer Research},
volume = {15},
number = {6},
year = {2026},
keywords = {},
abstract = {Background: Lung cancer accounts for the highest cancer-related mortality worldwide. Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) show significant efficacy in the treatment of lung cancer with EGFR mutations, but resistance inevitably occurs. Although immune checkpoint inhibitor treatment regimens have expanded post-resistance therapeutic options, head-to-head comparisons of diverse subsequent strategies and precise identification of beneficiary populations remain insufficient. This leads to inconsistent clinical decision-making. This study aimed to explore the efficacy of different subsequent treatment regimens and identify beneficiary populations for each regimen in patients at our center with resistance to third-generation EGFR-TKIs.Methods: The retrospective study enrolled 225 patients at Jiangsu Cancer Hospital from 2017 to 2023. All patients had pathologically confirmed EGFR-mutant lung adenocarcinoma and received multi-line subsequent treatment after third-generation EGFR-TKIs resistance. Patients were classified into an ICI (I+O) group (N=131) and a No ICIs group (N=94), further divided into immunotherapy plus bevacizumab plus chemotherapy (IBC), immunotherapy plus anlotinib (IA), immunotherapy plus chemotherapy (IC), bevacizumab plus chemotherapy (BC), chemotherapy alone (C), and Based on mutation subgroups. Baseline characteristics were compared using Chi-squared tests. Survival outcomes [progression-free survival (PFS), overall survival (OS)] were analyzed via Kaplan-Meier curves and log-rank tests. Multivariate Cox proportional hazards regression was used to adjust for potential confounding variables. Least absolute shrinkage and selection operator (LASSO) regression and Cox proportional hazard models were applied to screen prognostic factors. All follow-up data were analyzed using right-censoring methods. The cut-off date for the last follow-up was March 31, 2025.Results: The median progression-free survival (mPFS) of the I+O group (9.10 months) was significantly better than that of the No ICIs group (7.15 months, P23.9 kg/m2 (mPFS =9.00 months) derived the greatest treatment benefit.Conclusions: In conclusion, the IBC regimen presents a favorable PFS trend in real-world post-resistance management. Each sequential treatment corresponds to unique beneficiary baseline features. Individualized regimen selection may improve clinical prognosis. Given the single-center retrospective nature and limited sample size of certain subgroups, these observational trends require further validation in large-scale prospective studies.},
issn = {2226-4477}, url = {https://tlcr.amegroups.org/article/view/120026}
}