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.
- 1Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 2Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 3Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Abstract
Epidermal growth factor receptor exon 20 insertion mutations (EGFR ex20ins) define a rare, structurally heterogeneous subtype of non-small cell lung cancer (NSCLC) that is relatively insensitive to conventional EGFR tyrosine kinase inhibitors. Although amivantamab, sunvozertinib, zipalertinib, furmonertinib, and other EGFR ex20ins-directed agents have expanded treatment options in advanced disease, their role in resectable NSCLC remains undefined. This narrative review summarizes the biological and clinical characteristics of EGFR ex20ins and critically evaluates advanced-stage evidence and emerging perioperative strategies. PubMed, Web of Science, Scopus, Google Scholar, major preprint servers, oncology conference proceedings, trial registries, and regulatory sources were searched initially on June 3, 2026, with a targeted update on August 24, 2026. Peer-reviewed primary studies were prioritized; regulatory records, trial registries, conference abstracts, and preprints were included when they provided relevant emerging evidence. English- and Chinese-language publications were considered. EGFR ex20ins comprise heterogeneous insertion, duplication, and deletion-insertion variants with distinct conformational effects and drug sensitivity. Advanced-stage studies have established clinically relevant activity for EGFR/c-MET bispecific antibodies and novel EGFR ex20ins-directed tyrosine kinase inhibitors (TKIs), including randomized phase III progression-free survival (PFS) benefits for selected regimens. Perioperative studies are evaluating sunvozertinib, zipalertinib, furmonertinib, and amivantamab; however, evidence remains limited to ongoing trials, case reports, small series, and immature conference data, without mature randomized event-free survival (EFS), disease-free survival (DFS), or overall survival (OS) results. Advanced-stage evidence supports perioperative investigation but cannot establish benefit in resectable disease. Progress requires accurate variant-level testing and randomized trials defining pathological response, surgical feasibility, toxicity, central nervous system (CNS) control, DFS, and OS.
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BibTeX
@article{li2026perioperative,
title = {{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.}},
author = {Zhuoran Li and Yichao Han and Wenzhao Zhong and Hecheng Li},
journal = {Translational lung cancer research},
year = {2026},
month = sep,
doi = {10.21037/tlcr-2026-0848},
url = {https://europepmc.org/article/MED/42999608},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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.
AU - Zhuoran Li
AU - Yichao Han
AU - Wenzhao Zhong
AU - Hecheng Li
PY - 2026
DA - 2026/09/29
JO - Translational lung cancer research
DO - 10.21037/tlcr-2026-0848
UR - https://europepmc.org/article/MED/42999608
AB - Epidermal growth factor receptor exon 20 insertion mutations (EGFR ex20ins) define a rare, structurally heterogeneous subtype of non-small cell lung cancer (NSCLC) that is relatively insensitive to conventional EGFR tyrosine kinase inhibitors. Although amivantamab, sunvozertinib, zipalertinib, furmonertinib, and other EGFR ex20ins-directed agents have expanded treatment options in advanced disease, their role in resectable NSCLC remains undefined. This narrative review summarizes the biological and clinical characteristics of EGFR ex20ins and critically evaluates advanced-stage evidence and emerging perioperative strategies. PubMed, Web of Science, Scopus, Google Scholar, major preprint servers, oncology conference proceedings, trial registries, and regulatory sources were searched initially on June 3, 2026, with a targeted update on August 24, 2026. Peer-reviewed primary studies were prioritized; regulatory records, trial registries, conference abstracts, and preprints were included when they provided relevant emerging evidence. English- and Chinese-language publications were considered. EGFR ex20ins comprise heterogeneous insertion, duplication, and deletion-insertion variants with distinct conformational effects and drug sensitivity. Advanced-stage studies have established clinically relevant activity for EGFR/c-MET bispecific antibodies and novel EGFR ex20ins-directed tyrosine kinase inhibitors (TKIs), including randomized phase III progression-free survival (PFS) benefits for selected regimens. Perioperative studies are evaluating sunvozertinib, zipalertinib, furmonertinib, and amivantamab; however, evidence remains limited to ongoing trials, case reports, small series, and immature conference data, without mature randomized event-free survival (EFS), disease-free survival (DFS), or overall survival (OS) results. Advanced-stage evidence supports perioperative investigation but cannot establish benefit in resectable disease. Progress requires accurate variant-level testing and randomized trials defining pathological response, surgical feasibility, toxicity, central nervous system (CNS) control, DFS, and OS.
SN - 2218-6751
SN - 2226-4477
ER -