Antibody-drug conjugates in the perioperative treatment of resectable non-small cell lung cancer: a narrative review of research advances and prospects.
- 1Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide. Even after perioperative chemotherapy combined with immunotherapy, pathological complete response (pCR) rates remain below 30%, and further improvement in long-term outcomes has stalled. Antibody-drug conjugates (ADCs), leveraging targeted cytotoxicity and the bystander effect, can achieve tumor downstaging, micrometastasis clearance, and organ preservation in the perioperative setting, offering a new option beyond conventional chemoimmunotherapy. In this review, we aimed to summarize contemporary clinical evidence for perioperative ADCs in resectable non-small cell lung cancer (NSCLC) and to provide practical guidance on patient selection, toxicity management, and future research. We searched PubMed, Embase, Web of Science, and ClinicalTrials.gov, together with the abstract books of major oncology congresses [American Society of Clinical Oncology (ASCO), World Conference on Lung Cancer (WCLC), European Society for Medical Oncology (ESMO)], from January 1, 2018 to September 14, 2026 for English-language publications on ADCs in the perioperative treatment of resectable NSCLC. We included clinical trials, case reports, conference abstracts, guidelines, and authoritative reviews. Two authors independently screened and selected the literature; disagreements were resolved by consensus. Landmark studies published before 2018 were captured by reference-list screening. We cover TROP2-targeted agents (datopotamab deruxtecan, sacituzumab govitecan), HER2-directed trastuzumab deruxtecan, and bispecific EGFR-HER3 ADCs across neoadjuvant, adjuvant, and perioperative strategies, with attention to practice-changing platform trials such as NeoCOAST-2. Studies are grouped by therapeutic partner, namely ADCs combined with immune checkpoint inhibitors, ADCs combined with targeted agents, and ADCs administered as single agents in molecularly selected populations. We further examine how ADCs may substitute for, or complement, platinum-based chemotherapy, and how they interface with immune checkpoint inhibitors across the perioperative continuum. We discuss biomarker-guided patient selection, including TROP2 and HER2 expression and circulating tumor DNA (ctDNA)-based minimal residual disease (MRD); practical perioperative toxicity management (interstitial lung disease, oral mucositis, ocular and hematologic toxicity); and emerging mechanisms of ADC resistance. We also highlight future priorities, including MRD-directed, individualized adjuvant therapy and strategies to overcome resistance, to optimize ADC-based regimens for patients with suboptimal responses to standard treatment. ADCs should be positioned as a complement rather than a replacement for perioperative chemoimmunotherapy.
Related
- Perioperative treatment for resectable non-small cell lung cancer harboring EGFR exon 20 insertion mutations: a narrative review from advanced-stage evidence to whole-course precision management.
- Precision Perioperative Treatment for Resectable Non-Small Cell Lung Cancer: Current Status and Perspectives
- Adjuvant and Perioperative Systemic Therapy for Resectable Hepatocellular Carcinoma: Evidence, Biological Rationale, and Trial Design
- Immune checkpoint inhibitors across neoadjuvant, perioperative, and adjuvant settings for resectable non-small-cell lung cancer: a systematic review and meta-analysis of randomized trials
- Antibody peptide conjugates as multifunctional therapeutics: Mechanisms, challenges, and prospects.
BibTeX
@article{xiong2026antibodydrug,
title = {{Antibody-drug conjugates in the perioperative treatment of resectable non-small cell lung cancer: a narrative review of research advances and prospects.}},
author = {Ying Xiong and Lu Sun and Yi Peng},
journal = {Translational lung cancer research},
year = {2026},
month = sep,
doi = {10.21037/tlcr-2026-1066},
url = {https://europepmc.org/article/MED/42999616},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Antibody-drug conjugates in the perioperative treatment of resectable non-small cell lung cancer: a narrative review of research advances and prospects.
AU - Ying Xiong
AU - Lu Sun
AU - Yi Peng
PY - 2026
DA - 2026/09/28
JO - Translational lung cancer research
DO - 10.21037/tlcr-2026-1066
UR - https://europepmc.org/article/MED/42999616
AB - Lung cancer is the leading cause of cancer-related mortality worldwide. Even after perioperative chemotherapy combined with immunotherapy, pathological complete response (pCR) rates remain below 30%, and further improvement in long-term outcomes has stalled. Antibody-drug conjugates (ADCs), leveraging targeted cytotoxicity and the bystander effect, can achieve tumor downstaging, micrometastasis clearance, and organ preservation in the perioperative setting, offering a new option beyond conventional chemoimmunotherapy. In this review, we aimed to summarize contemporary clinical evidence for perioperative ADCs in resectable non-small cell lung cancer (NSCLC) and to provide practical guidance on patient selection, toxicity management, and future research. We searched PubMed, Embase, Web of Science, and ClinicalTrials.gov, together with the abstract books of major oncology congresses [American Society of Clinical Oncology (ASCO), World Conference on Lung Cancer (WCLC), European Society for Medical Oncology (ESMO)], from January 1, 2018 to September 14, 2026 for English-language publications on ADCs in the perioperative treatment of resectable NSCLC. We included clinical trials, case reports, conference abstracts, guidelines, and authoritative reviews. Two authors independently screened and selected the literature; disagreements were resolved by consensus. Landmark studies published before 2018 were captured by reference-list screening. We cover TROP2-targeted agents (datopotamab deruxtecan, sacituzumab govitecan), HER2-directed trastuzumab deruxtecan, and bispecific EGFR-HER3 ADCs across neoadjuvant, adjuvant, and perioperative strategies, with attention to practice-changing platform trials such as NeoCOAST-2. Studies are grouped by therapeutic partner, namely ADCs combined with immune checkpoint inhibitors, ADCs combined with targeted agents, and ADCs administered as single agents in molecularly selected populations. We further examine how ADCs may substitute for, or complement, platinum-based chemotherapy, and how they interface with immune checkpoint inhibitors across the perioperative continuum. We discuss biomarker-guided patient selection, including TROP2 and HER2 expression and circulating tumor DNA (ctDNA)-based minimal residual disease (MRD); practical perioperative toxicity management (interstitial lung disease, oral mucositis, ocular and hematologic toxicity); and emerging mechanisms of ADC resistance. We also highlight future priorities, including MRD-directed, individualized adjuvant therapy and strategies to overcome resistance, to optimize ADC-based regimens for patients with suboptimal responses to standard treatment. ADCs should be positioned as a complement rather than a replacement for perioperative chemoimmunotherapy.
SN - 2218-6751
SN - 2226-4477
ER -