Efficacy and safety of first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) combined with chemotherapy or antiangiogenic therapy as first-line treatment in patients with EGFR-mutant non-small cell lung cancer: A systematic review and meta-analysis

Objective: We conducted a meta-analysis to synthesize the results of published randomized controlled trials conducted to evaluate the efficacy and safety of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs) combined with chemotherapy or antiangiogenic therapy. Methods: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov databases were searched and literatures from international conferences were read to identify eligible studies. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). The secondary endpoints were disease control rate (DCR), overall survival (OS) and treatment-emergent adverse events (TEAEs). Results: 10 studies, all on first-generation EGFR-TKI combination therapy, involving 2367 patients were included. Combination therapy resulted in significant improvements in ORR (RR: 1.11, 95% CI: 1.06-1.17, P < 0.001), DCR (RR: 1.03, 95% CI: 1.01-1.05, P = 0.007), PFS (HR: 0.56, 95% CI: 0.51-0.62, P < 0.001), OS (HR: 0.74, 95% CI: 0.64-0.84, P = 0.002) over monotherapy. This improvement was more apparent in the EGFR-TKIs combination chemotherapy group, and indirect comparisons revealed that EGFR-TKIs combined with chemotherapy appeared to be superior to combined with antiangiogenic therapy in ORR (RR: 1.19, 95% CI: 1.07-1.32), DCR (RR: 1.04, 95% CI: 1.02-1.08), and OS (HR: 0.79, 95% CI: 0.66-0.96). Of additional concern is the increased incidence of TEAEs in combination therapy. Conclusion: As a first-line treatment for patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC), first-generation EGFR-TKIs combined with chemotherapy or antiangiogenic therapy was associated with significant improvement in ORR, DCR, PFS and OS compared with monotherapy.

Automated summary

The meta-analysis of randomized controlled trials showed that first-generation EGFR-TKIs combined with chemotherapy or antiangiogenic therapy led to significant improvements in objective response rate, disease control rate, progression-free survival, and overall survival compared to monotherapy in patients with EGFR-mutated advanced non-small cell lung cancer.