| アブストラクト | Safety data on MET inhibitors in patients with advanced NSCLC harboring MET exon 14 mutation and treated with frontline immune checkpoint inhibitors (ICIs) are still limited. Here, we describe clinical characteristics, liver biopsy features, and management of liver injury of two patients with a diagnosis of MET exon 14-mutant NSCLC receiving capmatinib after ICI failure. On the basis of histologic findings and exclusion of other potential causes, a diagnosis of drug-induced liver injury (DILI) associated with portal fibrosis was made in both cases. The use of hepatoprotective drugs, in addition to oral ursodeoxycholic acid, resulted in liver blood tests normalization. To provide a global safety perspective, we queried the Food and Drug Administration Adverse Event Reporting System and detected a robust disproportionality signal. Out of the 918 total reports with capmatinib from the Food and Drug Administration Adverse Event Reporting System database, DILI was recorded in 43 cases (4.7%), mostly serious (93.0%) with hospitalization and death recorded in 25.6% and 16.3% of the cases, respectively. The median time to onset was 42 days, with discontinuation and positive dechallenge documented in 41.9% and 39.5% of the cases, respectively. Anti-programmed cell death protein-1 agents were coreported in 11 DILI cases. Only two cases of DILI out of 105 reports were found for tepotinib. Our data support a potential association between capmatinib and DILI in patients who have also been previously exposed to immunotherapy. Considering the potential implications for sequence strategy and timing of ICI and MET inhibitor, further investigation is warranted. |
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| ジャーナル名 | JTO clinical and research reports |
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| 投稿日 | 2023/9/25 |
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| 投稿者 | Sisi, Monia; Vitale, Giovanni; Fusaroli, Michele; Riefolo, Mattia; Giunchi, Valentina; D'Errico, Antonietta; Ardizzoni, Andrea; Raschi, Emanuel; Gelsomino, Francesco |
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| 組織名 | Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna,;Italy.;Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum;University of Bologna, Bologna, Italy.;Internal Medicine Unit for the Treatment of Severe Organ Failure, Istituto di;Ricovero e Cura a Carattere (IRCCS) Azienda Ospedaliero-Universitaria di Bologna,;Bologna, Italy.;Pharmacology Unit, DIMEC, Alma Mater Studiorum University of Bologna, Bologna,;Department of Pathology, Istituto di Ricovero e Cura a Carattere (IRCCS) Azienda;Ospedaliero-Universitaria di Bologna, Bologna, Italy. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/37745898/ |
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