Efficacy and safety of antibody–drug conjugates in EGFR-mutated non-small cell lung cancer after EGFR-TKI resistance: a systematic review and meta-analysis

Abstract

Background Antibody–drug conjugates (ADCs) have emerged as potential treatment options for EGFR-mutated non-small cell lung cancer (NSCLC) after EGFR-tyrosine kinase inhibitor (TKI) resistance. We evaluated their efficacy and safety in this setting. Methods PubMed, Embase,and the Cochrane Library were searched for prospective clinical studies. Overlapping reports were assessed before endpoint-specific synthesis. Comparable proportional outcomes from non-randomized studies were pooled using random-effects models, whereas randomized controlled trials (RCTs) were summarized separately. Results Eight eligible clinical study reports were included. Four non-randomized reports contributed five independent underlying trial datasets; however, the ORR and DCR meta-analysis each included four non-overlapping analytical estimates because one pooled Dato-DXd estimate represented two underlying trial datasets that were not entered separately. The pooled ORR was 39.2%(95% CI,31.1%–48.0%),and the pooled DCR was 78.9%(95% CI,72.3%–84.2%).Three comparable non-overlapping datasets contributed to the grade ≥3 TEAE analysis, yielding a pooled incidence of 65.2%(95% CI,50.2%–77.7%),whereas four analytical datasets contributed to the ILD analysis, with a pooled reported incidence of 6.0%(95% CI,4.1%–8.5%).Two RCTs provided comparative evidence supporting sac-TMT, particularly for ORR and PFS. Conclusions ADCs showed antitumor activity after EGFR-TKI resistance, but efficacy and toxicity varied across platforms. Additional randomized trials and biomarker-informed studies are needed to define the optimal use of individual ADCs. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261288638, identifier CRD420261288638.