Successful treatment of an osimertinib-resistant lung adenocarcinoma with an exon 18 EGFR mutation (G719S) with afatinib plus bevacizumab
Abstract
Exon 18 mutations account for only 3.6% of EGFR mutations, and tumors with exon 18 mutations are often unresponsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We present a novel case of a lung adenocarcinoma with an exon 18 mutation resulting in a glycine to serine substitution at position 719 of the EGFR protein. The patient received osimertinib, a third generation EGFR-TKI, as the first-line treatment, but the disease progressed during treatment. Analysis of circulating free DNAs via next generation sequencing revealed TP53 mutations and EGFR and MET amplifications, as well as the exon 18 mutation. On the basis of these results, we administered afatinib, a second-generation TKI, and bevacizumab, a vascular endothelial growth factor inhibitor, as the second-line treatment. The patient's symptoms improved, and this treatment was continued for 12 months. This report suggests that afatinib plus bevacizumab can effectively treat osimertinib-refractory lung tumors with an exon 18 mutation.
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Structure-function-based grouping identified a larger subgroup of EGFR mutations, PACC mutants, for which second-generation TKIs were more selective than third-generation TKIs.
“While previous studies have shown activity of second-generation TKIs in patients with specific exon 18 mutations33,34, structure–function-based grouping identified a larger subgroup of EGFR mutations, PACC mutants, for which second-generation TKIs were more selective than third-generation TKIs.”
From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [33]
Cites
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“In recent NSCLC cases with common EGFR mutations, afatinib significantly improved progression-free survival (PFS), response rate, and time to failure and osimertinib significantly improved PFS and overall survival (OS) relative to gefitinib [5, 6].”
BackgroundYang, J. C.-H., Sequist, L. V., Geater, S. L., Tsai, C.-M., Mok, T. S. K., Schuler, M., Yamamoto, N., Yu, C.-J., Ou, S.-H. I., Zhou, C., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00026-1 · Cited by 1,002 · cited 4× · see citing works
“First, because our findings were derived from a single case report, further studies are warranted to confirm the efficacy of afatinib plus bevacizumab for treatment of osimertinib-refractory NSCLCs with uncommon EGFRmutations.”
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Structure-based classification predicts drug response in EGFR-mutant NSCLC
Robichaux, J. P., Le, X., Vijayan, R. S. K., Hicks, J. K., Heeke, S., Elamin, Y. Y., Lin, H. Y., Udagawa, H., Skoulidis, F., Tran, H., et al. (2021) · Nature · doi:10.1038/s41586-021-03898-1 · Cited by 490 · see citing works
- Authors
- Tamiya, M., Kunimasa, K., Nishino, K., Matsumoto, S., Kawachi, H., Kuno, K., Inoue, T., Kuhara, H., Imamura, F., Goto, K., & Kumagai, T.
- Affiliations
- Osaka International Cancer Institute (JP)
- National Cancer Center Hospital East (JP)
- Corresponding author
- Tamiya, Motohiro
- ORCID
- Venue
- Investigational New Drugs
- Published
- 2020-06-18
- Volume
- 39
- Issue
- 1
- Pages
- 232-236
- ISSN
- 0167-6997 (ISSN-L)
- 1573-0646
- OpenAlex
- W3036358937
- Cited by
- 5
- References
- 6
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 2
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Investigational New Drugs (publishedVersion)
- PubMed (publishedVersion)
- 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
- lung adenocarcinoma, osimertinib resistance, afatinib, bevacizumab, EGFR tyrosine kinase inhibitors, MET amplification, TP53 mutation, cell-free DNA, combination therapy, second-line therapy
- MeSH terms
- Bevacizumab, Adenocarcinoma of Lung, Afatinib, Acrylamides, Adult, Aniline Compounds, Antineoplastic Combined Chemotherapy Protocols, Exons, Humans, Indoles, Lung Neoplasms, Male, Mutation, Pyrimidines, Drug Resistance, Neoplasm, ErbB Receptors
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