High Incidence of C797S Mutation in Patients With Long Treatment History of EGFR Tyrosine Kinase Inhibitors Including Osimertinib
| Autor: | Atsushi Osoegawa, Tatsuma Asoh, Kosuke Kashiwabara, Taishi Harada, Takashi Miura, Kazuko Sakai, Ryotaro Morinaga, Kazuto Nishio, Takayuki Suetsugu, Masafumi Yamaguchi, Kenji Sugio, Kazuki Nabeshima, Kenichi Taguchi, Junji Kishimoto, Kentaro Tanaka, Tomomi Nakamura |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Oncology medicine.medical_specialty Disease medicine.disease_cause EGFR T790M Deep sequencing T790M Internal medicine Biopsy medicine Osimertinib Lung cancer RC254-282 Mutation medicine.diagnostic_test business.industry Cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens Targeted resequencing medicine.disease Original Article Acquired resistance business |
| Zdroj: | JTO Clinical and Research Reports, Vol 2, Iss 7, Pp 100191-(2021) JTO Clinical and Research Reports |
| ISSN: | 2666-3643 |
| Popis: | Introduction Although treatment with osimertinib confers survival benefits in patients with lung cancer with the EGFR T790M mutation, the mechanism of acquired resistance to osimertinib remains poorly understood. We conducted a prospective observational study to identify the mechanism on the basis of repeated tissue biopsies. Methods Patients with EGFR-mutated advanced lung cancer with a T790M mutation detected on a tissue biopsy underwent a rebiopsy after developing acquired resistance to osimertinib. Nucleic acids extracted from the biopsy samples were subjected to targeted resequencing (Oncomine Comprehensive Assay), and circulating cell-free DNA (ccfDNA) was analyzed by CAncer Personalized Profiling by deep Sequencing (AVENIO ctDNA Surveillance Kit). Results Between November 2016 and March 2020, a total of 87 patients were screened. Among them, 44 developed acquired resistance. Of these, 19 samples from rebiopsies and 12 from preosimertinib biopsies were able to be analyzed by an Oncomine Comprehensive Assay. A ccfDNA analysis was performed in 16 patients. Regarding the mechanisms of acquired resistance, structural change in EGFR, namely, C797S, G796S, or L792V, was the most frequent alteration, being observed in 57.9% of the cases. MET gain was observed in 31.6% of the cases, and gains in cell cycle genes were observed in 26.3% of the cases. In addition, we identified GAS6 gain and an ATM mutation in a patient with small-cell transformation and a BRAF V600E mutation in a patient with oligoprogressive disease. Conclusions A repeated tissue biopsy and a ccfDNA analysis were useful in analyzing the mechanisms underlying acquired resistance. A long treatment history of EGFR TKIs may result in a high percentage of EGFR structural change. |
| Databáze: | OpenAIRE |
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