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.
Keywords: Non-small cell lung cancer; adjuvant TKIs; meta-analysis; overall survival; resected.