Poor response to erlotinib in patients with tumors containing baseline EGFR T790M mutations found by routine clinical molecular testing
Open accessAbstract
Background EGFR T790M is the most common mutation associated with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Baseline EGFR T790M mutations in EGFR TKI-naïve patients have been reported, but the frequency and their association with response to EGFR TKIs remain unclear. Patients and methods The frequency of baseline EGFR T790M as detected by routine molecular genotyping was determined by reviewing clinical results obtained at our institution from 2009 to 2013. We also collected outcome data for treatment with EGFR TKIs. Results To define the incidence of EGFR T790M, we reviewed 2774 sequentially tested patients with lung cancer who underwent molecular testing using a mass spectrometry-based assay, and 11 (0.5%) had baseline EGFR T790M. Compiling results from several molecular techniques, we observed EGFR T790M in tumors from 20 patients who had not previously been treated with an EGFR TKI. In all cases, EGFR T790M occurred concurrently with another EGFR mutation, L858R (80%, 16/20), or exon 19 deletion (20%, 4/20). Two percent of all pre-treatment EGFR-mutant lung cancers harbored an EGFR T790M mutation. Thirteen patients received erlotinib monotherapy as treatment for metastatic disease. The response rate was 8% (1/13, 95% confidence interval 0%-35%). For the patients who received erlotinib, the median progression-free survival was 2 months and the median overall survival was 16 months. Conclusions De novo EGFR T790M mutations are rare (<1%) when identified by standard sensitivity methods. TKI therapy for patients with baseline EGFR T790M detected by standard molecular analysis has limited benefit.
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One study identified de novo T790M mutations more frequently within L858R tumors than within Del19 tumors among 20 EGFR TKI-naïve patients.
“One study identified de novo T790M mutations more frequently within L858R tumors than within Del19 tumors among 20 EGFR TKI-naïve patients”
From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [102]
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- Authors
- Yu, H. A., Arcila, M. E., Hellmann, M. D., Kris, M. G., Ladanyi, M., & Riely, G. J.
- Affiliations
- Weill Cornell Medicine (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Hellmann, M.D.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 25
- Issue
- 2
- Pages
- 423-428
- ISSN
- 0923-7534 (ISSN-L)
- PMC
- PMC3905781
- OpenAlex
- W2133283856
- Cited by
- 206
- References
- 3
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 9 · 2023: 15 · 2022: 15 · 2021: 17 · 2020: 16 · 2019: 20 · 2018: 19 · 2017: 35 · 2016: 22 · 2015: 13 · 2014: 8
- FWCI
- 20.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (P01CA129243)
- 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
- T790M mutation, erlotinib, EGFR tyrosine kinase inhibitors, acquired drug resistance, non-small cell lung cancer, L858R mutation, exon 19 deletion, treatment response, progression-free survival, molecular genotyping
- MeSH terms
- Erlotinib Hydrochloride, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, DNA Mutational Analysis, Female, Gene Frequency, Humans, Lung Neoplasms, Male, Middle Aged, Quinazolines, Retrospective Studies, Treatment Outcome, Disease-Free Survival, Drug Resistance, Neoplasm, Mutation, Missense, Genetic Association Studies, ErbB Receptors
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