Differential effects of adjuvant EGFR tyrosine kinase inhibitors in patients with different stages of non-small-cell lung cancer after radical resection: an updated meta-analysis

Di Lu,* Zhizhi Wang,* Xiguang Liu,* Siyang Feng, Xiaoying Dong, Xiaoshun Shi, He Wang, Hua Wu, Gang Xiong, Haofei Wang, Kaican Cai Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China *These authors contributed equally to this work Purpose: A survival improvement was achieved with adjuvant chemotherapy in non-small-cell lung cancer (NSCLC) patients, but its differential effects among patients with different stages remained controversial. This study aimed to compare the beneficial effects of adjuvant tyrosine kinase inhibitor (TKI) therapy with those of traditional therapy on NSCLC patients, specifically on EGFR-mutant and stage II–IIIA patients, who might benefit most from such treatment.Methods: MEDLINE, Embase, and the Cochrane Library were searched, and the results were screened independently according to certain criteria by two authors. Disease-free survival (DFS) and overall survival (OS) with HRs were used as the summary statistics.Results: A total of 2,915 publications were identified and screened. Six randomized control trials and three retrospective cohort studies of 2,467 patients with acceptable quality were included. The overall EGFR mutation rate was 48.62%. DFS was significantly improved in all the patients (HR, 0.77; 95% CI, 0.68–0.88) and in the subgroup of EGFR-mutant patients (HR, 0.49; 95% CI, 0.40–0.61). The difference of 5-year OS in the subgroup of EGFR-mutant patients (HR, 0.48; 95% CI, 0.31–0.72) was statistically significant, while in all the patients (HR, 1.01; 95% CI, 0.85–1.19), the difference was not significant. In the subgroups of studies in which 30% of patients were in stage IIIA (HR, 0.46; 95% CI, 0.35–0.60), DFS was significantly improved, while in the subgroups of studies in which 50% of patients were in stage I (HR, 0.90; 95% CI, 0.77–1.04), DFS was not significantly improved.Conclusion: Stage IIIA NSCLC patients might benefit more from adjuvant TKIs than stage I NSCLC patients after radical resection. Keywords: non-small-cell lung cancer, EGFR tyrosine kinase inhibitor, adjuvant therapy, meta-analysis