SynthesisFrontiers in immunology2026
Treatment prioritization of chemotherapy-anchored regimens after EGFR-TKI failure in EGFR-mutant NSCLC: a systematic review, pairwise meta-analysis and Bayesian network meta-analysis with probabilistic multi-criteria decision analysis.
Synthesis in Frontiers in immunology, 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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Abstract
Background: In advanced EGFR-mutant non-small cell lung cancer (NSCLC) after EGFR-TKI failure, chemotherapy alone offers limited benefit, while heterogeneous efficacy and safety across combination regimens complicate treatment selection. We systematically compared chemotherapy-anchored regimens in this setting to establish an evidence-informed treatment prioritization framework. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Cochrane Library, and oncology conference for randomized controlled trials evaluating patients with advanced EGFR-mutant NSCLC progressing after EGFR-TKI therapy, comparing experimental regimens (with or without chemotherapy) against platinum-based doublet chemotherapy (chemotherapy-anchored, chemo-anchored) for efficacy and safety outcomes. Primary outcomes were progression-free survival (PFS) and overall survival (OS), analyzed using hazard ratios (HRs). Fixed-effects pairwise meta-analyses and Bayesian random-effects network meta-analyses were performed to evaluate 8 treatment strategies: chemotherapy alone (Chemo, platinum-based doublet chemotherapy); chemotherapy plus immune checkpoint inhibitors (Chemo_ICI); chemotherapy plus anti-angiogenic therapy (Chemo_Antiangio); chemotherapy plus immune checkpoint inhibitors and anti-angiogenic therapy (Chemo_ICI_Antiangio); chemotherapy plus ivonescimab (Chemo_Ivo); sacTMT (sacituzumab tirumotecan); chemotherapy plus amivantamab (Chemo_Ami); and chemotherapy plus amivantamab and lazertinib (Chemo_Ami_Laz). Probabilistic multi-criteria decision analysis (pMCDA) integrated multi-criteria outcomes under three clinically informed weighting schemes (survival-focused, balanced, and safety-focused). All analyses were conducted using R software. Results: Eleven RCTs (n=3,606) were analyzed. In pairwise analyses versus Chemo, pooled results showed significant PFS benefit for Chemo_Ivo (HR 0.50, 95% CI 0.41-0.60), Chemo_ICI_Antiangio (HR 0.55, 95% CI 0.45-0.68), and Chemo_ICI (HR 0.77, 95% CI 0.67-0.88), while Chemo_Ivo also improved OS (HR 0.76, 95% CI 0.64-0.91). Under random-effects models, HR point estimates remained identical; significance was maintained in overall analyses but lost in several subgroups as confidence intervals encompassed 1. In network meta-analysis, Chemo_Ami_Laz (HR 0.44, 95% CrI 0.32-0.61), Chemo_Ami (HR 0.48, 95% CrI 0.33-0.70), sac-TMT (HR 0.49, 95% CrI 0.35-0.68), and Chemo_Ivo (HR 0.49, 95% CrI 0.38-0.64) showed the greatest PFS benefit versus Chemo. For OS, only sac-TMT (HR 0.60, 95% CrI 0.41-0.90) and Chemo_Ivo (HR 0.76, 95% CrI 0.60-0.98) were associated with a significant survival advantage. Chemo_Ami_Laz (OR 12.06, 95% CrI 3.64-53.50) and Chemo_Ami (OR 3.71, 95% CrI 1.12-12.19) were associated with a higher risk of grade ≥3 TRAEs. In pMCDA integrating efficacy and safety, sac-TMT, Chemo_Ami, and Chemo_Ivo consistently ranked as the top three strategies across all weighting schemes. Conclusion: Integrating efficacy and safety, sac-TMT, Chemo_Ami, and Chemo_Ivo appear to be the most favorable treatment options after EGFR-TKI failure in EGFR-mutant NSCLC. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251268510.
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