Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Dec;27(12):4405-4414.
doi: 10.1007/s12094-025-03971-5. Epub 2025 Jun 19.

Recommendations for diagnosis and management of non-small-cell lung carcinoma patients with ex20ins EGFR mutations: insights from a Delphi consensus

Dolores Isla  1 , Esther Conde  2   3   4 , Atocha Romero  5 , Margarita Garrido  6 , Juan Francisco Marín  7 , Bartomeu Massuti  8 , Ihab Abdulkader-Nallib  9   10 , María-Josep Carreras  11 , Marta Marina  12 , Jose M Calderón  12 , Ignacio Gil-Bazo  4   13   14
Affiliations
Review

Recommendations for diagnosis and management of non-small-cell lung carcinoma patients with ex20ins EGFR mutations: insights from a Delphi consensus

Dolores Isla et al. Clin Transl Oncol. 2025 Dec.

Abstract

Purpose: Patients with non-small-cell lung carcinoma (NSCLC) harboring exon 20 insertion (ex20ins) mutations in the epidermal growth factor receptor (EGFR) face a particularly poor prognosis. This consensus aimed to consolidate expert opinions on the diagnosis and management of these patients in view of recent advances in diagnostic and therapeutic approaches.

Methods: A comprehensive literature review was conducted to summarize evidence on managing NSCLC patients with ex20ins mutations. Using the Delphi methodology, the perspectives of 30 healthcare professionals (HCPs) from the Spanish National Healthcare System were collected regarding the diagnosis, therapeutic strategies, and patient perspectives of the disease.

Results: Experts emphasized the critical role of next-generation sequencing (NGS) in diagnosing NSCLC patients, highlighting the need for detailed molecular profiling to optimize therapeutic decisions. Amivantamab was identified as a potential preferred therapeutic option due to its demonstrated benefit in clinical trials, including patients with brain metastases. Additionally, the HCPs underscored the importance of incorporating patient-reported outcomes (PROs) into clinical evaluation and ensuring access to therapies with proven efficacy.

Conclusions: This consensus provides a valuable guideline for diagnosing and managing NSCLC patients with ex20ins EGFR mutations, emphasizing the integration of advanced diagnostic tools, evidence-based therapies, and patient-centered care to enhance clinical outcomes and improve patient quality of life.

Keywords: Amivantamab; EGFR; EGFR-TKI; Ex20ins; NGS; NSCLC.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: Dra. Isla reports consulting honoraria from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Beigene, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, Merck, MSD, Pfizer, Pharmamar, Sanofi, Takeda and speaker honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, F. Hoffmann-La Roche, Johnson & Johnson, Lilly, MSD, Pfizer, Pharmamar, and Takeda. Also institutional financial interests in clinical trials from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, F. Hoffmann-La Roche, GSK, Johnson & Johnson, Lilly, Merck, Mirati, MSD, Novartis, Pfizer, Pharmamar, Sanofi and research grants from AstraZeneca, BMS, F. Hoffmann-La Roche, and GSK. Dra. Conde reports serving in a consulting or advisory role for Johnson & Johnson, AstraZeneca, and Roche; receiving honoraria from Johnson & Johnson, AstraZeneca, Thermo Fisher, Roche, Lilly, and Pfizer; receiving research funding from Roche and Thermo Fisher. Dra. Romero has received the GECP grant sponsored by Janssen outside of the submitted work. Dra Garrido Siles reports serving in a consulting or advisory role for AstraZeneca, Takeda, and Roche: receiving support for attending meetings and/or travel from Roche, Merck Sharp & Dohme, and Novartis. Dr. Marin reports serving in a consulting or advisory role for Johnson & Johnson; receiving honoraria from Takeda, Daiichi Sankyo, Roche, AstraZeneca, and receiving support for attending meetings and/or Travel from Takeda, Merck Sharp & Dohme, Roche, Daiichi Sankyo and Boehringer Ingelheim. Dr. Massutí reports serving in a consulting or advisory role for Roche, BMS, Boehringer Ingelheim, Takeda, Beigene, Pharmamar and receiving support for attending meetings and/or travel from Roche, Pfizer, MSD, Astra-Zeneca. Dr. Abdulkader received honoraria for speaker, consultancy, or advisory role from Astra-Zeneca, Janssen, Merck-Serono, Roche, Pfizer, BMS, Lilly, Amgen, Astellas, MSD, and grant or travel support from Janssen, and Pfizer. Dra. Carreras reports serving in a consulting or advisory role, receiving honoraria from Johnson & Johnson; Novartis, Menarini Stemline España SLU, Jazz Pharmaceuticals, Takeda Pharmaceuticals international and Regeneron; and receiving support for attending meetings and/or Travel from Roche. Dra. Marina and Dr. Calderón are current employees of Johnson & Johnson. Dr. Gil-Bazo reports serving in a consulting or advisory role for Johnson & Johnson, Lilly, and Boehringer Ingelheim; receiving payment or honoraria from Johnson & Johnson, Amgen, AstraZeneca, Merck Sharp & Dohme, and Takeda; receiving support for attending meetings and/or travel from Johnson & Johnson, Merck Sharp & Dohme, Daiichi Sankyo, and Sanofi. The other authors declare that they have no conflict of interest. Ethical approval: This study did not involve patients or access to patient data and was conducted solely with healthcare professionals. Accordingly, it was exempt from formal ethics committee review in accordance with national regulations. Consent to participate: All participants received detailed information about the study's objectives and procedures. Informed consent was obtained by their voluntary completion of the first-round questionnaire.

References

    1. Basumallik N, Agarwal M. Small cell lung cancer. In StatPearls; StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC.: Treasure Island (FL) ineligible companies. Disclosure: Manuj Agarwal declares no relevant financial relationships with ineligible companies. 2024.
    1. Van Sanden S, Murton M, Bobrowska A, Rahhali N, Sermon J, Rodrigues B, et al. Prevalence of epidermal growth factor receptor exon 20 insertion mutations in non-small-cell lung cancer in europe: a pragmatic literature review and meta-analysis. Target Oncol. 2022;17:153–66. https://doi.org/10.1007/s11523-022-00868-z . - DOI - PubMed - PMC
    1. Bazhenova L, Minchom A, Viteri S, Bauml JM, Ou SI, Gadgeel SM, et al. Comparative clinical outcomes for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Lung Cancer. 2021;162:154–61. https://doi.org/10.1016/j.lungcan.2021.10.020 . - DOI - PubMed
    1. Ou S-HI, Hong J-L, Christopoulos P, Lin HM, Vincent S, Churchill EN, et al. Distribution and detectability of <em>EGFR</em> exon 20 insertion variants in NSCLC. J Thorac Oncol. 2023;18:744–54. https://doi.org/10.1016/j.jtho.2023.01.086 . - DOI - PubMed
    1. Wu J, Lin Z. Non-small cell lung cancer targeted therapy: drugs and mechanisms of drug resistance. Int J Mol Sci. 2022. https://doi.org/10.3390/ijms232315056 . - DOI - PubMed - PMC

LinkOut - more resources