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Natural History and Molecular Characteristics of Lung Cancers Harboring EGFR Exon 20 Insertions
Open accessAbstract
Introduction Exon 20 insertions are the third most common family of epidermal growth factor receptor (EGFR) mutations found in non-small-cell lung cancer (NSCLC). Little is known about cancers harboring these mutations aside from their lack of response to EGFR tyrosine kinase inhibitors, impairing the development of effective targeted therapies.Methods NSCLC patients with EGFR genotyping were studied using a mechanism approved by the Institutional Review Board. Cancers with exon 20 insertions were indentified, sequences were characterized, and effectiveness of different treatment regimens was reviewed retrospectively. Clinical characteristics and survival were compared with cancers harboring common EGFR mutations and cancers with wild-type EGFR.Results One thousand eighty-six patients underwent EGFR genotyping from 2004 to 2012. Twenty seven (2.5%) harbored exon 20 insertions, making up 9.2% of all cancers with documented EGFR mutations. Compared with wild-type cancers, those with exon 20 insertions were more commonly found in never-smokers and Asian patients. Insertion sequences were highly variable, with the most common variant (V769_D770insASV) making up only 22% of cases. Median survival of patients with exon 20 insertions was 16 months, similar to the survival of wild-type cancers and shorter than the survival of cancers with common EGFR mutations.Conclusions Patients with EGFR exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but a poorer prognosis. The prevalence of this subset of NSCLC is similar to that of other genotype-defined subsets of lung adenocarcinoma (e.g. those with BRAF mutations, HER2 insertions, ROS1 rearrangements) and is a population of interest for trials of new targeted therapies.
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“they are typically unresponsive to first and second-generation EGFR TKIs due to the modified structures of their kinase domains”
From Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC (2018) · cites this paper as [6]
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“and are associated with a similar overall survival of EGFR wild type patients [71].”
In the citing paper
“This sequence alteration accounts for 10–20% of all reported EGFR exon 20 insertions 31,32,35.”
From Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer (2013) · cites this paper as [31]
In the citing paper
“The most common EGFR exon 20 insertions that have been reported in NSCLC samples are post C-helix insertions of one to four amino-acids, which in aggregate account for 80–90% of all exon 20 insertions 31,32,35.”
From Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer (2013) · cites this paper as [31]
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“Therefore, patients with NSCLC harboring EGFR exon 20 insertion mutations present a shorter survival time compared to patients with classic EGFR mutations [21].”
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Cites
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Mok, T. S., Wu, Y.-L., Thongprasert, S., Yang, C.-H., Chu, D.-T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810699 · Cited by 8,261 · cited 1×
“The identification of epidermal growth factor receptor (EGFR) mutations in a subset of non–small-cell lung cancer (NSCLC) and their association with durable responses to EGFR tyrosine kinase inhibitors (TKIs) has transformed our approach towards the use of targeted therapies in treating lung cancer.(1,2) This initial…”
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Kwak, E. L., Bang, Y., Camidge, D. R., Shaw, A. T., Solomon, B., Maki, R. G., Ou, S. I., Dezube, B. J., Janne, P. A., Costa, D. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1006448 · Cited by 4,477
Inhibition of Mutated, Activated BRAF in Metastatic Melanoma
Flaherty, K. T., Puzanov, I., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. A., O'Dwyer, P. J., Lee, R. J., Grippo, J. F., Nolop, K., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002011 · Cited by 3,103
Shigematsu, H., Lin, L., Takahashi, T., Nomura, M., Suzuki, M., Wistuba, I. I., Fong, K. M., Lee, H., Toyooka, S., Shimizu, N., et al. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji055 · Cited by 2,377
Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer
Rosell, R., Moran, T., Queralt, C., Porta, R., Cardenal, F., Camps, C., Majem, M., Lopez-Vivanco, G., Isla, D., Provencio, M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0904554 · Cited by 2,373
Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma
Flaherty, K. T., Robert, C., Hersey, P., Nathan, P., Garbe, C., Milhem, M. M., Демидов, Л. В., Hassel, J. C., Rutkowski, P. L., Mohr, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1203421 · Cited by 2,205
ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers
Bergethon, K., Shaw, A. T., Ignatius Ou, S.-H., Katayama, R., Lovly, C. M., McDonald, N. T., Massion, P. P., Siwak-Tapp, C., Gonzalez, A., Fang, R., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.6345 · Cited by 1,555
Improved survival with MEK Inhibition in BRAF-mutated melanoma for the METRIC Study Group
Flaherty, K. T., Robert, C., Hersey, P., Nathan, P., Garbe, C., Milhem, M. M., Демидов, Л. В., Hassel, J. C., Rutkowski, P. L., Mohr, P., et al. (2012) · Zurich Open Repository and Archive (University of Zurich) · doi:10.5167/uzh-63198 · Cited by 1,330
Mutations of the Epidermal Growth Factor Receptor Gene in Lung Cancer
Kosaka, T., Yatabe, Y., Endoh, H., Kuwano, H., Takahashi, T., & Mitsudomi, T. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2818 · Cited by 1,220
Clinical Characteristics of Patients With Lung Adenocarcinomas Harboring BRAF Mutations
Paik, P. K., Arcila, M. E., Fara, M. G., Sima, C. S., Miller, V. A., Kris, M. G., Ladanyi, M., & Riely, G. J. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.1280 · Cited by 692
Somatic Mutations of the HER2 Kinase Domain in Lung Adenocarcinomas
Shigematsu, H., Takahashi, T., Nomura, M., Majmudar, K., Suzuki, M., Lee, H., Wistuba, I. I., Fong, K. M., Toyooka, S., Shimizu, N., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4235 · Cited by 678
Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants
Greulich, H., Chen, T.-H., Feng, W., Jänne, P. A., Alvarez, J. V., Zappaterra, M., Bulmer, S. E., Frank, D. A., Hahn, W. C., Sellers, W. R., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020313 · Cited by 677
Oxnard, G. R., Arcila, M. E., Sima, C. S., Riely, G. J., Chmielecki, J., Kris, M. G., Pao, W., Ladanyi, M., & Miller, V. A. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2692 · Cited by 627
Self-citationYasuda, H., Kobayashi, S., & Costa, D. B. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70129-2 · Cited by 610
Mitsudomi, T., & Yatabe, Y. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00607.x · Cited by 606
Jackman, D. M., Yeap, B. Y., Sequist, L. V., Lindeman, N., Holmes, A. J., Joshi, V. A., Bell, D. W., Huberman, M. S., Halmos, B., Rabin, M. S., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0462 · Cited by 584
Self-citationArcila, M. E., Chaft, J. E., Nafa, K., Roy-Chowdhuri, S., Lau, C., Zaidinski, M., Paik, P. K., Zakowski, M. F., Kris, M. G., & Ladanyi, M. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0912 · Cited by 505
Wu, J.-Y., Wu, S.-G., Yang, C.-H., Gow, C.-H., Chang, Y.-L., Yu, C.-J., Shih, J.-Y., & Yang, P.-C. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5123 · Cited by 319
Perera, S. A., Li, D., Shimamura, T., Raso, M. G., Ji, H., Chen, L., Borgman, C. L., Zaghlul, S., Brandstetter, K. A., Kubo, S., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808930106 · Cited by 189
Jänne, P. A., Boss, D. S., Camidge, D. R., Britten, C. D., Engelman, J. A., Garon, E. B., Guo, F., Wong, S., Liang, J., Letrent, S., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1220 · Cited by 181
Shimamura, T., Perera, S. A., Foley, K. P., Sang, J., Rodig, S. J., Inoue, T., Chen, L., Li, D., Carretero, J., Li, Y.-C., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2967 · Cited by 167
Association of KRAS and EGFR mutations with survival in patients with advanced lung adenocarcinomas
Johnson, M. L., Sima, C. S., Chaft, J., Paik, P. K., Pao, W., Kris, M. G., Ladanyi, M., & Riely, G. J. (2013) · Cancer · doi:10.1002/cncr.27730 · Cited by 166
EGFR Exon 19 Insertions: A New Family of Sensitizing EGFR Mutations in Lung Adenocarcinoma
He, M., Capelletti, M., Nafa, K., Yun, C.-H., Arcila, M. E., Miller, V. A., Ginsberg, M. S., Zhao, B., Kris, M. G., Eck, M. J., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2361 · Cited by 149
Self-citationEGFR exon 20 insertion mutation in Japanese lung cancer
Sasaki, H., Endo, K., Takada, M., Kawahara, M., Kitahara, N., Tanaka, H., Okumura, M., Matsumura, A., Iuchi, K., Kawaguchi, T., et al. (2007) · Lung Cancer · doi:10.1016/j.lungcan.2007.06.024 · Cited by 84
Clinical Outcomes in Non–Small Cell Lung Cancers Harboring Different Exon 19 Deletions in EGFR
Chung, K.-P., Wu, S.-G., Wu, J.-Y., Yang, J. C.-H., Yu, C.-J., Wei, P.-F., Shih, J.-Y., & Yang, P.-C. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2353 · Cited by 72
Rare Cancer Trial Design: Lessons from FDA Approvals
Gaddipati, H., Liu, K., Pariser, A., & Pazdur, R. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1135 · Cited by 63
Xu, W., Soga, S., Beebe, K. L., Lee, M.-J., Kim, Y. S., Trepel, J. B., & Neckers, L. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603950 · Cited by 44
Garon, E. B., Morán, T., Barlési, F., Gandhi, L., Sequist, L. V. D., Kim, S., Groen, H. J. M., Besse, B., Smit, E. F., Kim, D., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.30.15_suppl.7543 · Cited by 44
Yatabe, Y., Pao, W. J., & Jett, J. R. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318251980b · Cited by 20
Costa, D. B., Yasuda, H., Sng, N., Yeo, W.-L., de Figueiredo‐Pontes, L. L., Tenen, D. G., & Kobayashi, S. S. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.30.15_suppl.7523 · Cited by 6
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Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs
Kris, M. G., Johnson, B. E., Berry, L. D., Kwiatkowski, D. J., Iafrate, A. J., Wistuba, I. I., Varella-Garcia, M., Franklin, W. A., Aronson, S. L., Su, P.-F., et al. (2014) · JAMA · doi:10.1001/jama.2014.3741 · Cited by 1,724
Self-citationNon–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology
Ettinger, D. S., Wood, D. E., Aisner, D. L., Akerley, W., Bauman, J. R., Chirieac, L. R., D’Amico, T. A., DeCamp, M. M., Dilling, T. J., Dobelbower, M. C., et al. (2017) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2017.0050 · Cited by 1,315
Gridelli, C., Rossi, A., Carbone, D. P., Guarize, J., Karachaliou, N., Mok, T. S. K., Petrella, F., Spaggiari, L., & Rosell, R. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.9 · Cited by 1,146
The quest to overcome resistance to EGFR-targeted therapies in cancer
Chong, C. R., & Janne, P. A. (2013) · Nature Medicine · doi:10.1038/nm.3388 · Cited by 1,076
Metadata
- Authors
- Oxnard, G. R., Lo, P. C., Nishino, M., Dahlberg, S. E., Lindeman, N. I., Butaney, M., Jackman, D. M., Johnson, B. E., & Jänne, P. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Oxnard, Geoffrey R.
- ORCID
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 8
- Issue
- 2
- Pages
- 179-184
- ISSN
- 1556-0864 (ISSN-L)
- PMC
- PMC3549533
- OpenAlex
- W2075445339
- Cited by
- 360
- References
- 32
- Citations by year
- 2026: 17 · 2025: 30 · 2024: 33 · 2023: 41 · 2022: 50 · 2021: 36 · 2020: 31 · 2019: 26 · 2018: 24 · 2017: 19 · 2016: 16 · 2015: 15 · 2014: 15 · 2013: 7
- FWCI
- 14.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5k23ca157631-02)
- National Cancer Institute (K23-CA157631, P50CA090578, R01CA135257)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- EGFR exon 20 insertion, non-small cell lung cancer, lung adenocarcinoma, EGFR mutation, EGFR tyrosine kinase inhibitors, survival, never smokers, Asian patients, targeted therapy, molecular properties
- MeSH terms
- Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Exons, Female, Follow-Up Studies, Humans, Lung Neoplasms, Male, Middle Aged, Molecular Sequence Data, Mutation, Neoplasm Staging, Prognosis, Retrospective Studies, Survival Rate, Mutagenesis, Insertional, Sequence Homology, Amino Acid, Young Adult, ErbB Receptors
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