PMID- 32068351 OWN - NLM STAT- MEDLINE DCOM- 20210311 LR - 20220603 IS - 1759-7714 (Electronic) IS - 1759-7706 (Print) IS - 1759-7706 (Linking) VI - 11 IP - 4 DP - 2020 Apr TI - Severe hepatotoxicity due to osimertinib after nivolumab therapy in patients with non-small cell lung cancer harboring EGFR mutation. PG - 1045-1051 LID - 10.1111/1759-7714.13363 [doi] AB - BACKGROUND: Osimertinib is the most promising treatment option for patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) with acquired T790M resistance. However, recent studies have suggested that osimertinib could increase the frequency of serious adverse events (AEs) if administered immediately after immune checkpoint inhibitor (ICI) treatment. METHODS: In this single-institution retrospective study conducted from May 2016 to January 2019, osimertinib was administered to 47 patients with pretreated advanced NSCLC harboring the EGFR mutation. RESULTS: Of the 47 patients, 20 (42.6%) were men and 27 (57.4%) were women. The median age was 71 years (range 37-83 years). A total of 19 patients (40.4%) had a smoking history. Furthermore, seven patients (14.9%) received osimertinib immediately after nivolumab therapy, while 40 patients (85.1%) were treated with osimertinib after treatment with drugs other than nivolumab. The frequency of grade 3 or 4 hepatotoxicity was significantly higher in patients with nivolumab prior to osimertinib (4/7; 57.1%) than in those treated with drugs other than nivolumab prior to osimertinib (2/40; 5.0%) (P = 0.0026). Liver biopsies were performed in two patients who received osimertinib immediately after nivolumab. In both patients, CD-8-positive T cell infiltration was predominantly observed in the liver tissues. CONCLUSIONS: The use of osimertinib immediately after nivolumab significantly increased the frequency of grade 3 or higher hepatotoxicity in patients with advanced NSCLC harboring EGFR mutation acquired T790M resistance. CI - (c) 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. FAU - Yamaguchi, Ou AU - Yamaguchi O AUID- ORCID: 0000-0001-7194-6459 AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Kaira, Kyoichi AU - Kaira K AUID- ORCID: 0000-0001-5548-7686 AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Kawasaki, Tomonori AU - Kawasaki T AD - Department of Pathology, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Mouri, Atsuto AU - Mouri A AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Hashimoto, Kosuke AU - Hashimoto K AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Shiono, Ayako AU - Shiono A AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Shinomiya, Shun AU - Shinomiya S AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Miura, Yu AU - Miura Y AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Nishihara, Fuyumi AU - Nishihara F AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Murayama, Yoshitake AU - Murayama Y AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Kobayashi, Kunihiko AU - Kobayashi K AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. FAU - Mochida, Satoshi AU - Mochida S AD - Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan. FAU - Kagamu, Hiroshi AU - Kagamu H AD - Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20200218 PL - Singapore TA - Thorac Cancer JT - Thoracic cancer JID - 101531441 RN - 0 (Acrylamides) RN - 0 (Aniline Compounds) RN - 31YO63LBSN (Nivolumab) RN - 3C06JJ0Z2O (osimertinib) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Acrylamides/administration & dosage MH - Adult MH - Aged MH - Aged, 80 and over MH - Aniline Compounds/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology MH - Case-Control Studies MH - Chemical and Drug Induced Liver Injury/etiology/*pathology MH - ErbB Receptors/genetics MH - Female MH - Follow-Up Studies MH - Humans MH - Lung Neoplasms/*drug therapy/genetics/pathology MH - Male MH - Middle Aged MH - *Mutation MH - Nivolumab/administration & dosage MH - Prognosis MH - Retrospective Studies MH - Survival Rate PMC - PMC7113047 OTO - NOTNLM OT - Hepatotoxicity OT - immune checkpoint inhibitor OT - nivolumab OT - non-small-cell lung cancer OT - osimertinib EDAT- 2020/02/19 06:00 MHDA- 2021/03/12 06:00 PMCR- 2020/04/01 CRDT- 2020/02/19 06:00 PHST- 2019/12/08 00:00 [received] PHST- 2020/02/03 00:00 [revised] PHST- 2020/02/05 00:00 [accepted] PHST- 2020/02/19 06:00 [pubmed] PHST- 2021/03/12 06:00 [medline] PHST- 2020/02/19 06:00 [entrez] PHST- 2020/04/01 00:00 [pmc-release] AID - TCA13363 [pii] AID - 10.1111/1759-7714.13363 [doi] PST - ppublish SO - Thorac Cancer. 2020 Apr;11(4):1045-1051. doi: 10.1111/1759-7714.13363. Epub 2020 Feb 18.