Objectives: Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways have demonstrated promising results for treatment of advanced non-small cell lung cancer (NSCLC). We conducted a systematic review and meta-analysis to assess the efficacy and toxicity of the combined treatment with EGFR tyrosine kinase inhibitors (TKIs) and VEGF blockade for patients with advanced NSCLC harboring activating EGFR mutations, in comparison to EGFR TKIs alone.Methods: The electronic databases PubMed (Medline), Cochrane Library and EMBASE, were searched for relevant randomized trials between 2000 and 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and grade ≥ 3 adverse events (AEs). Pooled hazard ratios (HR) for OS and PFS, and odds ratios (OR) for ORR, DCR and toxicity were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. Subgroup analyses compared PFS by gender, age, smoking status, EGFR mutation, intra-cranial disease and Eastern Cooperative Oncology Group (ECOG) status.Results: A total of 1,246 patients from 6 trials were evaluated for analyses. The combination treatment decreased the risk of disease progression by 38% (HR=0.62; 95%CI=0.53-0.72) but had no added benefit on OS compared to EGFR inhibition alone (HR=0.93; 95%CI=0.74-1.17). There was no significant difference in ORR or DCR between treatments. There was a significantly increased number of AEs reported in the dual treatment arm (OR=4.41; 95%CI=2.33-8.37), with proteinuria and hypertension being the most significantly increased AEs. The PFS benefit was consistent across all subgroups. Conclusions: This meta-analysis suggests combined inhibition of EGFR and VEGF pathways significantly improves PFS, with no interim OS benefit, and increases AEs. Mature OS data are needed along with results from trials exploring this strategy with 3rd generation EGFR-TKIs to strengthen these results.