Disease-free survival improved by use of adjuvant EGFR tyrosine kinase inhibitors in resectable non-small cell lung cancer: an updated meta-analysis

Abstract

Background: A previous meta-analysis of our research team suggested survival advantage from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after surgery in patients with EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to follow up on the findings of the previous one and presents our latest updates through the past few years.

Methods: The study advanced the previous meta-analysis and included a comprehensive range of relevant studies in PubMed. Disease-free survival (DFS) with hazard ratios (HRs) was calculated using random and/or fixed-effects models. Subgroup analysis and meta-regression analysis were also performed.

Results: A total of 2,223 patients in seven studies were eligible for the analysis. Adjuvant EGFR-TKIs administration was significantly associated with superior DFS [HR, 0.60; 95% confidence interval (CI), 0.42-0.87], corresponding to an absolute benefit of 3.4% at 3 years, yet with significant heterogeneity (I²=80.0%, P <0.001). EGFR mutation rate of included patients was found to be a source of heterogeneity by meta-regression analysis (P=0.005). In the EGFR-mutant sub-population, HR for DFS was 0.51 (95% CI, 0.39-0.65), corresponding to an absolute benefit of 7.1% at 3 years. The rate of overall grade 3 or greater adverse events (AEs) was 38.9% (95% CI, 35.9-41.9%).

Conclusions: The updated meta-analysis provided strengthened evidence of significant DFS advantage of adjuvant EGFR-TKI treatment for patients with EGFR-mutant NSCLC after complete resection.

Keywords: Epidermal growth factor receptor (EGFR); adjuvant treatment; lung cancer; survival; tyrosine kinase inhibitor (TKI).

Figure 1

Flow diagram showing the study selection.

Figure 2

All patients: (A) forest plot of HR for DFS with adjuvant EGFR-TKIs treatment verse control. HR for individual trials and overall effect are given with 95% CI; (B) estimated disease-free survival curves. HR, hazard ratio; DFS, disease-free survival; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitors; CI, confidence interval.

Figure 3

EGFR-mutant subgroup: (A) forest plot of HR for DFS with adjuvant EGFR-TKIs treatment verse control. HR for individual trials and overall effect are given with 95% CI; (B) estimated disease-free survival curves. HR, hazard ratio; DFS, disease-free survival; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitors; CI, confidence interval.