{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:24:35Z","timestamp":1780514675993,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tom and Catherine Cully Charitable Trust to Banner MD Anderson Cancer Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background and Clinical Significance: Non-small-cell lung cancer (NSCLC) with EGFR mutations, particularly de novo compound mutations such as exon 19 deletions (Ex19del) with T790M substitutions, present a significant clinical challenge due to resistance to many treatments. While treating these patients, the administration of osimertinib, a third-generation EGFR inhibitor, after immunotherapy can lead to unique immune-related adverse events (irAEs), such as pneumonitis and, rarely, hepatitis. Case Presentation: A 36-year-old Filipino woman presented with metastatic NSCLC harboring de novo Ex19del and T790M mutations. Despite initial therapy with carboplatin and paclitaxel, followed by chemoimmunotherapy, the patient\u2019s disease progressed. She subsequently developed severe hepatitis from osimertinib after her prior immunotherapy with pembrolizumab. After the hepatitis resolved with high-dose steroids, osimertinib was switched to afatinib, but her disease rapidly progressed with new metastases. A second attempt at osimertinib rechallenge, with concomitant prednisone, resulted in substantial disease control, including improved leptomeningeal disease (LMD) and no recurrence of hepatitis. Conclusions: This case underscores the feasibility of rechallenging with osimertinib in patients who experience adverse events such as hepatotoxicity, provided that appropriate management strategies, such as steroid therapy, are employed. The successful rechallenge in this case highlights the potential of osimertinib as a viable option in advanced EGFR-mutant NSCLC, even after prior treatment-related complications.<\/jats:p>","DOI":"10.3390\/reports8030101","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T11:15:23Z","timestamp":1750936523000},"page":"101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Osimertinib-Induced Hepatitis Following Immunotherapy in a Patient with Lung Adenocarcinoma Harboring De Novo EGFR Exon 19 Deletion and T790M Mutations: A Case Report"],"prefix":"10.3390","volume":"8","author":[{"given":"Bradley","family":"Steiner","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine Phoenix, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Edmond","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Banner M.D. Anderson Cancer Center, Gilbert, AZ 85234, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Camou","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Banner M.D. Anderson Cancer Center, Gilbert, AZ 85234, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9908-3251","authenticated-orcid":false,"given":"Taylor","family":"Praska","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Banner M.D. Anderson Cancer Center, Gilbert, AZ 85234, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-287X","authenticated-orcid":false,"given":"Jiaxin","family":"Niu","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Banner M.D. Anderson Cancer Center, Gilbert, AZ 85234, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"78985","DOI":"10.18632\/oncotarget.12587","article-title":"The Prevalence of EGFR Mutation in Patients with Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/cncr.29812","article-title":"Role of Race in Oncogenic Driver Prevalence and Outcomes in Lung Adenocarcinoma: Results from the Lung Cancer Mutation Consortium","volume":"122","author":"Steuer","year":"2016","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"497","DOI":"10.18632\/oncotarget.186","article-title":"EGFR-Mutated Lung Cancer: A Paradigm of Molecular Oncology","volume":"1","author":"Zhang","year":"2010","journal-title":"Oncotarget"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"i3","DOI":"10.1093\/annonc\/mdx702","article-title":"Overview of Current Systemic Management of EGFR-Mutant NSCLC","volume":"29","author":"Hsu","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41571-024-00971-2","article-title":"The Changing Treatment Landscape of EGFR-Mutant Non-Small-Cell Lung Cancer","volume":"22","author":"Zhou","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1093\/annonc\/mdz077","article-title":"Severe Immune-Related Adverse Events Are Common with Sequential PD-(L)1 Blockade and Osimertinib","volume":"30","author":"Schoenfeld","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.21037\/tlcr-22-235","article-title":"Multiple Mutations in the EGFR Gene in Lung Cancer: A Systematic Review","volume":"11","author":"Chaves","year":"2022","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100791","DOI":"10.1016\/j.tranon.2020.100791","article-title":"Molecular Characteristics and Clinical Outcomes of EGFR Exon 19 C-Helix Deletion in Non-Small Cell Lung Cancer and Response to EGFR TKIs","volume":"13","author":"Xu","year":"2020","journal-title":"Transl. Oncol."},{"key":"ref_9","first-page":"10","article-title":"T790M and Acquired Resistance of EGFR TKI: A Literature Review of Clinical Reports","volume":"3","author":"Ma","year":"2011","journal-title":"J. Thorac. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/JTO.0b013e3181913c9f","article-title":"EGFR T790M Mutation: A Double Role in Lung Cancer Cell Survival?","volume":"4","author":"Suda","year":"2009","journal-title":"J. Thorac. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1056\/NEJMoa1913662","article-title":"Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC","volume":"382","author":"Ramalingam","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1056\/NEJMoa1612674","article-title":"Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer","volume":"376","author":"Mok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1021\/acs.biochem.0c00104","article-title":"Insight into the Therapeutic Selectivity of the Irreversible EGFR Tyrosine Kinase Inhibitor Osimertinib through Enzyme Kinetic Studies","volume":"59","author":"Zhai","year":"2020","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"61","DOI":"10.21037\/atm.2018.12.68","article-title":"Central Nervous System Activity of First-Line Osimertinib in Epidermal Growth Factor Receptor-Mutant Advanced Non-Small Cell Lung Cancer","volume":"7","author":"Liam","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/1759-7714.13363","article-title":"Severe Hepatotoxicity Due to Osimertinib after Nivolumab Therapy in Patients with Non-small Cell Lung Cancer Harboring EGFR Mutation","volume":"11","author":"Yamaguchi","year":"2020","journal-title":"Thorac. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kalra, A., and Rashdan, S. (2023). The Toxicity Associated with Combining Immune Check Point Inhibitors with Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1158417"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1007\/s00262-023-03429-z","article-title":"Incidence of Serious Adverse Events Caused by Tyrosine Kinase Inhibitor Treatment Following Immune Checkpoint Inhibitor Therapy in Advanced NSCLC Patients with Oncogenic Driver Alterations","volume":"72","author":"Shimoda","year":"2023","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"O\u2019Reilly, D., O\u2019Leary, C.L., Reilly, A., Teo, M.Y., O\u2019Kane, G., Hendriks, L., Bennett, K., and Naidoo, J. (2024). Toxicity of Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitor Combinations in Solid Tumours: A Systematic Review and Meta-Analysis. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1380453"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1016\/j.jtho.2017.01.026","article-title":"Successful Osimertinib Rechallenge after Severe Osimertinib-Induced Hepatotoxicity","volume":"12","author":"Yoshida","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1007\/s10637-018-0608-7","article-title":"Successful Oral Desensitization with Osimertinib Following Osimertinib-Induced Fever and Hepatotoxicity: A Case Report","volume":"36","author":"Hirabayashi","year":"2018","journal-title":"Investig. New Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1158\/1535-7163.MCT-16-0407","article-title":"Characterization of EGFR T790M, L792F, and C797S Mutations as Mechanisms of Acquired Resistance to Afatinib in Lung Cancer","volume":"16","author":"Kobayashi","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1158\/1078-0432.CCR-22-1585","article-title":"Leptomeningeal Metastasis from Non\u2013Small Cell Lung Cancer and Current Landscape of Treatments","volume":"29","author":"Ozcan","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1016\/S1470-2045(17)30689-7","article-title":"Leptomeningeal Metastases in Non-Small-Cell Lung Cancer","volume":"19","author":"Cheng","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1200\/JCO.19.00457","article-title":"Osimertinib in Patients with Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study","volume":"38","author":"Yang","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1200\/JCO.24.00708","article-title":"Phase II Efficacy and Safety of 80 Mg Osimertinib in Patients with Leptomeningeal Metastases Associated with Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer (BLOSSOM)","volume":"42","author":"Park","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12964-023-01082-8","article-title":"Toward the next Generation EGFR Inhibitors: An Overview of Osimertinib Resistance Mediated by EGFR Mutations in Non-Small Cell Lung Cancer","volume":"21","author":"Li","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13045-016-0290-1","article-title":"EGFR C797S Mutation Mediates Resistance to Third-Generation Inhibitors in T790M-Positive Non-Small Cell Lung Cancer","volume":"9","author":"Wang","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/j.jtho.2017.08.006","article-title":"Combination Osimertinib and Gefitinib in C797S and T790M EGFR-Mutated Non-Small Cell Lung Cancer","volume":"12","author":"Arulananda","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1200\/JCO.21.00662","article-title":"Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study","volume":"39","author":"Park","year":"2021","journal-title":"J. Clin. Oncol."}],"container-title":["Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2571-841X\/8\/3\/101\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:59:27Z","timestamp":1760032767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2571-841X\/8\/3\/101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,26]]},"references-count":30,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["reports8030101"],"URL":"https:\/\/doi.org\/10.3390\/reports8030101","relation":{},"ISSN":["2571-841X"],"issn-type":[{"value":"2571-841X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,26]]}}}