EGFR inhibitors as adjuvant therapy for resected non-small cell lung cancer harboring EGFR mutations

Objectives: Cisplatin-based chemotherapy as an adjuvant therapy for resected non-small cell lung cancer (NSCLC) has reached its plateau, and it is limited by a high risk of recurrence and significant toxicities. The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected NSCLC harboring EGFR mutations remains controversial. In this study, we performed a meta-analysis to evaluate the role of EGFR inhibitors as an adjuvant therapy for targeted patients. Materials and methods: Studies were identified via electronic search. The pooled odds ratio (OR) for disease-free survival (DFS) and overall survival (OS) were calculated for the meta-analysis. Results: There were 11 trials (1,152 resected NSCLC patients with EGFR sensitive mutations) in this meta analysis. The results showed that adjuvant treatment with EGFR-TKIs can prolong both the OS and DFS when compared to treatment without TKIs as an adjuvant therapy (OS: OR, 0.63; 95% CI, 0.46 to 0.87, P = 0.004; heterogeneity I-2 = 61%, P = 0.008; DFS: OR, 0.56; 95% CI, 0.43 to 0.72, P < 0.00001; heterogeneity I-2 = 37%, P = 0.10). The results of the predefined subgroup analyses in this meta-analysis suggested a greater DFS with the mono EGFR-TKIs compared with chemotherapy, whereas the OS benefit failed to show a similar difference between the two arms (p = 0.30). We also found that treatment with EGFR-TKIs plus chemotherapy was associated with a significantly longer DFS and OS compared to mono chemotherapy in patients with completely resected EGFR-mutant NSCLC (DFS: OR, 0.48; 95% CI, 0.34-0.68; P < 0.0001; heterogeneity I-2 = 47%, P = 0.07; OS: OR, 0.50; 95% CI, 0.31-0.78; P = 0.003; heterogeneity I-2 = 57%, P = 0.05). Additionally, less severe adverse events (SAES) were observed in the TKIs group (OR, 0.22; 95% Cl, 0.14 to 0.37, P < 0.00001; heterogeneity I-2 = 22%, P = 0.28). Conclusion: The addition of EGFR-TKIs to adjuvant chemotherapy can prolong the OS and PFS for resected NSCLC. Adjuvant EGFR-TKIs may be a potential treatment option compared to adjuvant chemotherapy in completely resected patients with EGFR mutation-positive NSCLC. Statement of significance: The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected non-small cell lung cancer (NSCLC) harboring EGFR mutations remains controversial. This study demonstrates that EGFR-TKIs as an adjuvant therapy could prolong the DFS and potentially prolong the OS in postoperative patients. Therefore, this therapy paves the way for EGFR-TKIs to be an adjuvant treatment for NSCLC.