SynthesisScientific reports2026
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.
Synthesis in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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9 authors.
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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 estimates for PFS (HR, 0.52; 95% CI, 0.44-0.61) and iPFS (HR, 0.36; 95% CI, 0.25-0.52). RCT-only analyses most consistently supported the PFS benefit of EGFR-TKI plus chemotherapy; OS rankings were less definitive, and randomized iPFS evidence remained sparse. Radiotherapy-related results were exploratory because the radiotherapy node pooled WBRT, SRS/SRT, mixed approaches, and variable dose-fractionation schedules. EGFR-TKI plus chemotherapy showed the most consistent evidence for delaying progression. The apparent OS advantage of EGFR-TKI plus anti-angiogenic therapy, and findings for radiotherapy- and bispecific antibody-based combinations, should be interpreted cautiously. Treatment selection should be individualized according to treatment goals, EGFR-TKI generation, intracranial disease burden, expected toxicity, and patient tolerability.
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