A systematic review and network meta-analysis of first-line EGFR-TKI-based combination strategies for EGFR-mutant non-small cell lung cancer with brain metastases
Abstract
Brain metastases are common in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) and remain clinically challenging despite the improved central nervous system activity of third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs). Because direct comparisons between active first-line combination strategies are limited, this systematic review and network meta-analysis (NMA) evaluated the relative efficacy and safety of EGFR-TKI-based combinations in this population. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to December 31, 2025. Randomized controlled trials (RCTs) and non-randomized comparative studies were eligible if they enrolled patients with EGFR-mutated NSCLC and brain metastases and compared EGFR-TKI monotherapy with EGFR-TKI-based combinations incorporating chemotherapy, anti-angiogenic therapy, radiotherapy, or bispecific antibody therapy. Bayesian NMAs were performed for overall survival (OS), progression-free survival (PFS), and intracranial PFS (iPFS). RCT-only analyses were conducted as robustness assessments. Grade ≥ 3 treatment-related adverse events (TRAEs) were summarized descriptively. Forty-eight studies involving 5,432 patients were included, of which 17 were RCTs. In the overall network, EGFR-TKI plus anti-angiogenic therapy showed the most favorable OS estimate versus monotherapy (HR, 0.63; 95% CI, 0.49-0.80), whereas EGFR-TKI plus chemotherapy showed the most favorable…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 5,432 participants or records.
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