EGFR tyrosine kinase inhibitor plus angiogenesis inhibitor combination therapy in treatment-naïve <i>EGFR</i> -mutant advanced non–small cell lung cancer: A systematic review and meta-analysis.

Abstract

e20754 Background: The benefit of adding angiogenesis inhibitors to EGFR-TKIs in treatment naive EGFR mutant NSCLC remains controversial. We conducted an updated meta analysis to evaluate efficacy and safety. Methods: We searched PubMed, Embase, Cochrane Library, and oncology conferences through January 2026 for RCTs comparing EGFR TKI plus angiogenesis inhibitor versus EGFR TKI alone in treatment-naïve EGFR mutant advanced NSCLC. Primary endpoint was PFS. Random effects meta analyses with Hartung Knapp adjustment were performed. Risk of bias was assessed using RoB 2.0; certainty using GRADE. Results: Thirteen RCTs enrolling 2,580 patients were included. Combination therapy significantly improved PFS (HR 0.65, 95% CI 0.60-0.71; p &lt; 0.0001; I² = 0%). Median PFS ranged from 13.7-24.8 months versus 8.2-20.2 months in controls. PFS benefit was consistent across subgroups: exon 19 deletion (HR 0.59), L858R (HR 0.64), brain metastases present (HR 0.59) or absent (HR 0.63), and across angiogenesis inhibitor classes. OS was not improved (HR 0.97, 95% CI 0.87-1.07). Combination therapy increased toxicity: grade ≥3 AEs (RR 1.53), hypertension (RR 6.30), and proteinuria (RR 10.56). GRADE certainty was high for PFS benefit and absence of OS benefit. Conclusions: EGFR TKI plus angiogenesis inhibitor significantly prolongs PFS but does not improve OS and increases toxicity. These findings provide high certainty evidence to guide shared decision making in the first line setting. Key subgroup analyses for PFS. Subgroup HR 95% CI I² Overall (13 studies) 0.65 0.60–0.71 0% Exon 19 deletion 0.59 0.49–0.71 0% L858R mutation 0.64 0.52–0.79 0% Brain mets present 0.59 0.46–0.74 0% Brain mets absent 0.63 0.53–0.76 0% Phase III trials 0.64 0.59–0.70 0%