{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:50:48Z","timestamp":1760244648102,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Linkou Chang Gung Memorial Hospital","award":["CMRPG3M0971","CMRPG3K0601","NSTC 109-2314-B-182-080-MY3"],"award-info":[{"award-number":["CMRPG3M0971","CMRPG3K0601","NSTC 109-2314-B-182-080-MY3"]}]},{"name":"National Science and Technology Council","award":["CMRPG3M0971","CMRPG3K0601","NSTC 109-2314-B-182-080-MY3"],"award-info":[{"award-number":["CMRPG3M0971","CMRPG3K0601","NSTC 109-2314-B-182-080-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epidermal growth factor receptor (EGFR) triple mutations with exon 19 deletion (del19), T790M, and cis-C797S (del19\/T790M\/cis-C797S mutations) frequently occur in patients with non-small cell lung cancer (NSCLC), while progression to frontline EGFR-tyrosine kinase inhibitors (TKIs) and osimertinib was resistant to all clinically available EGFR-TKIs. Brigatinib monotherapy may be a potential treatment for NSCLC harboring del19\/T790M\/cis-C797S mutations based on preclinical studies; however, no clinical report has evaluated its efficacy on EGFR del19\/T790M\/cis-C797S mutations. Herein, we present a case of a female patient with EGFR del19-mutated NSCLC treated with afatinib followed by osimertinib due to acquired T790M mutation. The EGFR del19\/T790M\/cis-C797S mutations were detected following osimertinib treatment. Complete response of skull metastasis was confirmed after brigatinib treatment (90 mg daily). Unfortunately, she experienced intolerable adverse events; therefore, brigatinib was discontinued after three-month usage. This report provides the first reported evidence for the use of brigatinib monotherapy in patients with NSCLC harboring EGFR del19\/T790M\/cis-C797S mutations after progression to previous EGFR-TKIs.<\/jats:p>","DOI":"10.3390\/ijms24010602","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T03:26:11Z","timestamp":1672370771000},"page":"602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Response to Brigatinib Targeted Therapy in Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 19 Deletion, T790M, and cis-C797S Triple Mutations: A Case Report"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7904-2614","authenticated-orcid":false,"given":"Zi-Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333423, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-1058","authenticated-orcid":false,"given":"Gigin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging & Intervention, Clinical Metabolomics Core, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333423, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsuan-Jen","family":"Shih","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333423, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1081-8805","authenticated-orcid":false,"given":"Chiao-En","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333423, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nrc2088","article-title":"Epidermal growth factor receptor mutations in lung cancer","volume":"7","author":"Sharma","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S1470-2045(14)71173-8","article-title":"Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): Analysis of overall survival data from two randomised, phase 3 trials","volume":"16","author":"Yang","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1470-2045(13)70604-1","article-title":"Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): An open-label, randomised phase 3 trial","volume":"15","author":"Wu","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrclinonc.2014.104","article-title":"Acquired resistance to TKIs in solid tumours: Learning from lung cancer","volume":"11","author":"Camidge","year":"2014","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.21873\/anticanres.15697","article-title":"Real-world Afatinib Outcomes in Advanced Non-small Cell Lung Cancer Harboring EGFR Mutations","volume":"42","author":"Chen","year":"2022","journal-title":"Anticancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Tang, Y.J., Chang, J.W.C., Chang, C.F., Huang, C.Y., Yang, C.T., Kuo, C.H.S., Fang, Y.F., Hsu, P.C., and Wu, C.E. (2022). Impact of T790M Mutation Status on Later-Line Osimertinib Treatment in Non-Small Cell Lung Cancer Patients. Cancers, 14.","DOI":"10.3390\/cancers14205095"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.3389\/fonc.2020.01481","article-title":"An Observational Study of Acquired EGFR T790M-Dependent Resistance to EGFR-TKI Treatment in Lung Adenocarcinoma Patients in Taiwan","volume":"10","author":"Wu","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chang, Z.-T., Chan, T.-M., and Wu, C.-E. (2022). EGFR T751_I759delinsN Mutation in Exon19 Detected by NGS but Not by Real-Time PCR in a Heavily-Treated Patient with NSCLC. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113451"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17534666221132731","DOI":"10.1177\/17534666221132731","article-title":"Sequential treatment in advanced non-small cell lung cancer harboring EGFR mutations","volume":"16","author":"Hsu","year":"2022","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1056\/NEJMoa1411817","article-title":"AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer","volume":"372","author":"Yang","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41416-019-0573-8","article-title":"Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer","volume":"121","author":"Leonetti","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14768","DOI":"10.1038\/ncomms14768","article-title":"Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer","volume":"8","author":"Uchibori","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"875313","DOI":"10.3389\/fonc.2022.875313","article-title":"Case Report: Durable Response to the Combination of Brigatinib and Cetuximab Plus Icotinib in a NSCLC Patient Harboring EGFR L858R-T790M-cis-G796S and L718Q Resistance Mutations Following Progression With Osimertinib","volume":"12","author":"Wang","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1158\/1078-0432.CCR-17-2310","article-title":"Investigating Novel Resistance Mechanisms to Third-Generation EGFR Tyrosine Kinase Inhibitor Osimertinib in Non\u2013Small Cell Lung Cancer PatientsNovel Resistance Mechanisms to Osimertinib in NSCLC Patients","volume":"24","author":"Yang","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1001\/jamaoncol.2018.2969","article-title":"Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib","volume":"4","author":"Oxnard","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1016\/j.jtho.2020.04.014","article-title":"Effective Treatment of Lung Adenocarcinoma Harboring EGFR-Activating Mutation, T790M, and cis-C797S Triple Mutations by Brigatinib and Cetuximab Combination Therapy","volume":"15","author":"Wang","year":"2020","journal-title":"J. Thorac. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/602\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:55:30Z","timestamp":1760147730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,29]]},"references-count":16,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010602"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010602","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,12,29]]}}}