The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
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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Park, S., Lee, S. Y., Kim, D., Sim, Y. S., Ryu, J.-S., Choi, J., Lee, S. H., Ryu, Y. J., Lee, J. H., & Chang, J. H. (2021) · Figshare · doi:10.6084/m9.figshare.13559872
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He, Q., Cheng, Y., Zhang, Q., Xiang, H., Fan, N., Yang, X., Tao, J., Qi, C., 李云霞, Zhou, S., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01760
Targeted Therapies for EGFR Exon 20 Insertion Mutations in Non-Small Cell Lung Cancer
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BindingDB (2024) · UC San Diego · doi:10.7270/q2cv4p5p
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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