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
- 1Zhejiang Chinese Medical University
- 2First Hospital of Jiaxing, Jiaxing
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.
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BibTeX
@article{chen2026efficacy,
title = {{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}},
author = {Yilin Chen and Shuaixuan Chen and Hang Zhang and Jiebo Xie and Binbin Song and Yufen Xu},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1909040},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1909040/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Yilin Chen
AU - Shuaixuan Chen
AU - Hang Zhang
AU - Jiebo Xie
AU - Binbin Song
AU - Yufen Xu
PY - 2026
DA - 2026/10/14
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1909040
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1909040/full
AB - 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.
SN - 2234-943X
ER -