Rational Application of First-Line EGFR-TKIs Combined with Antiangiogenic Inhibitors in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

purposeA meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors (A + T) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC).

methodsPubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ≥ 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs).

resultsData were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone (HR = 0.60;

conclusionAddition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.