Efficacy of Adjuvant First-Generation TKIs versus Chemotherapy in Patients with Completely Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Meta-Analysis

Abstract

Background The use of adjuvant first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) in patients with resected EGFR-mutant non-small cell lung cancer (NSCLC) remains controversial. Therefore, we performed a systematic review with meta-analysis to investigate the overall survival (OS) in patients with resected NSCLC. Methods Relevant studies were identified from the PubMed and EMBASE databases, and pooled hazard risks were obtained by random-effects models. Results Three prospective phase III and one phase II randomized controlled trials were identified, including a total of 839 patients who had undergone resection of EGFR-sensitive mutation in our analysis, 429 of whom received adjuvant first-generation TKIs therapy. For all patients with complete resection, adjuvant first-generation TKIs therapy was associated with improved disease-free survival (DFS) [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.30–0. 82] but not OS (HR: 0.78, 95% CI: 0.48–1.27) compared with adjuvant chemotherapy. In addition, we reconstructed the OS curves of the ADJUVANT and IMPACT studies, and the pooled 3- and 5-year OS rates of stage II-III patients in the TKI group and chemotherapy group were 80% vs. 79% and 66% vs. 64%, respectively. We also reconstructed the DFS curves based on the ADJUVANT, IMPACT, and EVIDENCE studies, and the pooled 1-, 3- and 5-year DFS rates of stage II-III patients in the TKI group and chemotherapy group were 87% vs. 70%, 49% vs. 37% and 28% vs. 29%, respectively. Conclusions In patients with completely resected EGFR-mutant NSCLC, adjuvant first-generation TKIs may delay disease progression but still fail to improve long-term survival compared with conventional chemotherapy.