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Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: Clinical outcomes and response to erlotinib
Open accessAbstract
BACKGROUND: Epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins) represent approximately 10% of EGFR-mutant lung adenocarcinomas, and are associated with resistance to EGFR tyrosine kinase inhibitors (TKIs). Clinical outcomes in comparison with patients with sensitizing EGFR mutations are not well established. METHODS: Patients with stage IV lung adenocarcinomas with EGFR exon20ins were identified through routine molecular testing. Clinicopathologic data were collected. Overall survival (OS) was measured from the diagnosis of stage IV disease, and in patients treated with EGFR TKIs, the time to progression (TTP) on erlotinib was measured. RESULTS: One thousand eight hundred and eighty-two patients with stage IV lung adenocarcinomas were identified: 46 patients had EGFR exon20ins (2%), and 258 patients had an EGFR exon 19 deletion (exon19del)/L858R point mutation (14%). Among 11 patients with lung adenocarcinomas with EGFR exon20ins who received erlotinib, 3 patients (27%) had a partial response (FQEA, 1; ASV, 1; and unknown variant, 1). TTP for patients with EGFR exon20ins and patients with EGFR exon19del/L858R on erlotinib were 3 and 12 months, respectively (P < .01). Responses to chemotherapy were similar for patients with lung adenocarcinomas with EGFR exon20ins and patients with lung adenocarcinomas with EGFR exon19del/L858R. Median OS from the diagnosis of stage IV disease for patients with EGFR exon20ins and patients with EGFR exon19del/L858R was 26 months (95% confidence interval, 19 months-not reached n = 46) and 31 months (95% confidence interval, 28-33 months; n = 258), respectively (P = .53). CONCLUSIONS: The majority of patients with advanced lung adenocarcinomas harboring EGFR exon20ins do not respond to EGFR TKI therapy. Standard chemotherapy should be used as first-line therapy. These patients have an OS similar to that of patients with sensitizing EGFR mutations. Individuals with certain variants such as FQEA and ASV may respond to erlotinib.
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In the citing paper
“Available treatment outcomes demonstrated lack of response to first- and second-generation EGFR TKIs such as erlotinib, gefitinib and afatinib, consistent with other series”
From Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC (2018) · cites this paper as [19]
In the citing paper
“A review of 84 patients with exon 20 insertions across different series treated with either gefitinib or erlotinib demonstrated a RR of only 11% with a PFS of 2.4 months (12).”
From Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors (2017) · cites this paper as [12]
In the citing paper
“EGFR Ex20Ins tumors are generally unresponsive to 1st and 2nd generation EGFR inhibitors”
From Antitumor Activity of Osimertinib, an Irreversible Mutant-Selective EGFR Tyrosine Kinase Inhibitor, in NSCLC Harboring EGFR Exon 20 Insertions (2018) · cites this paper as [6]
In the citing paper
“These patients may experience a higher overall response rate (ORR) (58–63%) and a longer PFS (six months) with platinum-doublet chemotherapy, as reported in small retrospective studies [70,71].”
In the citing paper
“Patients harboring exon 20 insertions are associated with an ORR of 0–11% and a median progression-free survival (PFS) of 2–3 months when treated with first- or second-generation EGFR TKIs [19,21,37,44,45,70]”
In the citing paper
“Several studies, although very small, have shown that 1G EGFR‐TKI are less effective in patients with NSCLC harboring such uncommon EGFR mutations, compared with patients harboring common EGFR mutations.”
In the citing paper
“In a compilation of data on the treatment response to 1G‐TKI, ORR was only 17% (10/59) (Table 3).61, 62, 63, 64, 65”
From Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy (2016) · cites this paper as [62]
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Cites
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486
EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368
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
Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR
Maemondo, M., Inoue, A., Kobayashi, K., Sugawara, S., Oizumi, S., Isobe, H., Gemma, A., Harada, M., Yoshizawa, H., Kinoshita, I., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0909530 · Cited by 5,525
Rosell, R., Carcereny, E., Gervais, R., Vergnenegre, A., Massuti, B., Felip, E., Palmero, R., Garcia-Gomez, R., Pallares, C., Sanchez, J. M., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70393-x · Cited by 5,489
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338
Self-citationMitsudomi, T., Morita, S., Yatabe, Y., Negoro, S., Okamoto, I., Tsurutani, J., Seto, T., Satouchi, M., Tada, H., Hirashima, T., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70364-x · Cited by 4,090
Zhou, C., Wu, Y.-L., Chen, G., Feng, J., Liu, X.-Q., Wang, C., Zhang, S., Wang, J., Zhou, S., Ren, S., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70184-x · Cited by 4,081
Sequist, L. V., Yang, J. C.-H., Yamamoto, N., O'Byrne, K., Hirsh, V., Mok, T., Geater, S. L., Orlov, S., Tsai, C.-M., Boyer, M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.2806 · Cited by 3,228
Scagliotti, G. V., Parikh, P., von Pawel, J., Biesma, B., Vansteenkiste, J., Manegold, C., Serwatowski, P., Gatzemeier, U., Digumarti, R., Zukin, M., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.0375 · Cited by 3,203
Yu, H. A., Arcila, M. E., Rekhtman, N., Sima, C. S., Zakowski, M. F., Pao, W., Kris, M. G., Miller, V. A., Ladanyi, M., & Riely, G. J. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2246 · Cited by 2,454
Self-citationUsing 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-citationMutations 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
LKB1 modulates lung cancer differentiation and metastasis
Ji, H., Ramsey, M. R., Hayes, D. N., Fan, C., McNamara, K., Kozlowski, P., Torrice, C., Wu, M. C., Shimamura, T., Perera, S. A., et al. (2007) · Nature · doi:10.1038/nature06030 · Cited by 1,064
Han, J.-Y., Park, K., Kim, S.-W., Lee, D. H., Kim, H. Y., Kim, H. T., Ahn, M. J., Yun, T., Ahn, J. S., Suh, C., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.36.8456 · Cited by 736
Yasuda, H., Park, E., Yun, C.-H., Sng, N. J., Lucena-Araujo, A. R., Yeo, W.-L., Huberman, M. S., Cohen, D. W., Nakayama, S., Ishioka, K., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007205 · Cited by 571
Self-citationCosta, D. B., Halmos, B., Kumar, A., Schumer, S., Huberman, M. S., Boggon, T. J., Tenen, D. G., & Kobayashi, S. S. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040315 · Cited by 511
Arcila, M. E., Nafa, K., Chaft, J. E., Rekhtman, N., Lau, C., Reva, B. A., Zakowski, M. F., Kris, M. G., & Ladanyi, M. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0620 · Cited by 473
Self-citationA murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response
Chen, Z., Cheng, K., Walton, Z., Wang, Y., Ebi, H., Shimamura, T., Liu, Y., Tupper, T., Ouyang, J., Li, J., et al. (2012) · Nature · doi:10.1038/nature10937 · Cited by 446 · cited 1×
“In KRAS-mutant tumors, the presence of a concurrent liver kinase B1 (serine/ threonine kinase 11) mutation portends a poor prognosis, and may confer resistance to targeted therapies such as mammalian target of rapamycin (mTOR) and mitogenactivated protein kinase (MEK) kinase inhibition.(31-37) Two of our 3 patients wi…”
BackgroundYang, J. C., Shih, J., Su, W., Hsia, T., Tsai, C., Ou, S. I., Yu, C., Chang, G., Ho, C., Sequist, L. V. D., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70086-4 · Cited by 413
Rekhtman, N., Paik, P. K., Arcila, M. E., Tafe, L. J., Oxnard, G. R., Moreira, A. L., Travis, W. D., Zakowski, M. F., Kris, M. G., & Ladanyi, M. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2109 · Cited by 361
Self-citationNatural History and Molecular Characteristics of Lung Cancers Harboring EGFR Exon 20 Insertions
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. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182779d18 · Cited by 360
Oxnard, G. R., Arcila, M. E., Chmielecki, J., Ladanyi, M., Miller, V. A., & Pao, W. J. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2571 · Cited by 359
Self-citationBeau-Faller, M., Prim, N., Ruppert, A.-M., Nanni-Metéllus, I., Lacave, R., Lacroix, L., Escande, F., Lizard, S., Pretet, J.-L., Rouquette, I., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdt418 · Cited by 324
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
Prevalence and specificity of LKB1 genetic alterations in lung cancers
Matsumoto, S., Iwakawa, R., Takahashi, K., Kohno, T., Nakanishi, Y., Matsuno, Y., Suzuki, K., Nakamoto, M., Shimizu, E., Minna, J. D., et al. (2007) · Oncogene · doi:10.1038/sj.onc.1210418 · Cited by 284
Pan, Q., Pao, W. J., & Ladanyi, M. (2005) · Journal of Molecular Diagnostics · doi:10.1016/s1525-1578(10)60569-7 · Cited by 245
Self-citationCarretero, J., Shimamura, T., Rikova, K., Jackson, A. L., Wilkerson, M. D., Borgman, C. L., Buttarazzi, M., Sanofsky, B. A., McNamara, K. L., Brandstetter, K. A., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.04.026 · Cited by 245
Ludovini, V., Bianconi, F., Pistola, L., Chiari, R., Minotti, V., Colella, R., Giuffrida, D., Tofanetti, F. R., Siggillino, A., Flacco, A., et al. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31820a3a6b · Cited by 180
Su, Z., Dias-Santagata, D., Duke, M., Hutchinson, K., Lin, Y.-L., Borger, D. R., Chung, C. H., Massion, P. P., Vnencak-Jones, C. L., Iafrate, A. J., et al. (2011) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2010.11.010 · Cited by 176 · cited 2×
“Positive cases were characterized via Sanger sequencing with the primers FW1:50-CATTCA TGCGTCTTCACCTG-30 and REV1:50-GTATA GGGGTACCGTTTGAG-30.”
MethodKoivunen, J. P., Kim, J., Lee, J., Rogers, A. M., Park, J. O., Zhao, X., Naoki, K., Okamoto, I., Nakagawa, K., Yeap, B. Y., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604469 · Cited by 168
Fukuyama, Y., Mitsudomi, T., Sugio, K., Ishida, T., Akazawa, K., & Sugimachi, K. (1997) · British Journal of Cancer · doi:10.1038/bjc.1997.194 · Cited by 145
Arrieta, O. G., Cardona, A. F., Corrales, L., Campos-Parra, A. D., Sánchez-Reyes, R., Amieva-Rivera, E., Rodríguez, J. K., Vargas, C. A., Carranza, H., Otero, J. M., et al. (2014) · Lung Cancer · doi:10.1016/j.lungcan.2014.12.009 · Cited by 88
EGFR 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
Mutations of p53 and K-ras genes as prognostic factors for non-small cell lung cancer.
Huang, C., Taki, T., Adachi, M., Konishi, T., Higashiyama, M., Kinoshita, M., Hadama, T., & Miyake, M. (1998) · International Journal of Oncology · doi:10.3892/ijo.12.3.553 · Cited by 72
Clinicopathological Characteristics of 11 NSCLC Patients with EGFR-Exon 20 Mutations
Lund‐Iversen, M., Kleinberg, L., Fjellbirkeland, L., Helland, Å., & Brustugun, O. T. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182614a9d · Cited by 62
Lammers, P. E., Lovly, C. M., & Horn, L. (2014) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2014.0002 · Cited by 15
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Metadata
- Authors
- Naidoo, J., Sima, C. S., Rodriguez, K., Busby, N., Nafa, K., Ladanyi, M., Riely, G. J., Kris, M. G., Arcila, M. E., & Yu, H. A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine Memorial Sloan Kettering Cancer Center New York New York
- Department of Pathology Memorial Sloan Kettering Cancer Center New York New York
- Corresponding author
- Naidoo, Jarushka
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2015-06-10
- Volume
- 121
- Issue
- 18
- Pages
- 3212-3220
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- PMC
- PMC4807634
- OpenAlex
- W1566300951
- Cited by
- 211
- References
- 37
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 17 · 2023: 19 · 2022: 29 · 2021: 34 · 2020: 28 · 2019: 13 · 2018: 21 · 2017: 11 · 2016: 10 · 2015: 2
- FWCI
- 11.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P01CA129243, P30CA008748, T32CA009207, R25CA020449)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- EGFR exon 20 insertion, lung adenocarcinoma, erlotinib, EGFR tyrosine kinase inhibitors, EGFR exon 19 deletion, L858R mutation, EGFR mutation, treatment resistance, overall survival, time to progression, first-line chemotherapy, advanced lung cancer, clinical outcomes, molecular testing, targeted therapy response
- MeSH terms
- Erlotinib Hydrochloride, Adenocarcinoma of Lung, Adenocarcinoma, Aged, Antineoplastic Agents, Exons, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutagenesis, Insertional, Treatment Outcome, Genes, erbB-1, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, Kaplan-Meier Estimate
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