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 dis-proportionality 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.(c) 2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND li-cense (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Capmatinib-Induced Liver Injury as Emerging Toxicity of MET Inhibitors in Patients With NSCLC Pretreated With Immune Checkpoint Inhibitors / Sisi, Monia; Vitale, Giovanni; Fusaroli, Michele; Riefolo, Mattia; Giunchi, Valentina; D’Errico, Antonietta; Ardizzoni, Andrea; Raschi, Emanuel; Gelsomino, Francesco. - In: JTO CLINICAL AND RESEARCH REPORTS. - ISSN 2666-3643. - ELETTRONICO. - 4:9(2023), pp. 100563.1-100563.8. [10.1016/j.jtocrr.2023.100563]

Capmatinib-Induced Liver Injury as Emerging Toxicity of MET Inhibitors in Patients With NSCLC Pretreated With Immune Checkpoint Inhibitors

Sisi, Monia
Primo
;
Vitale, Giovanni;Fusaroli, Michele;Riefolo, Mattia;Giunchi, Valentina;D’Errico, Antonietta;Ardizzoni, Andrea;Raschi, Emanuel
Ultimo
;
Gelsomino, Francesco
2023

Abstract

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 dis-proportionality 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.(c) 2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND li-cense (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).
2023
Capmatinib-Induced Liver Injury as Emerging Toxicity of MET Inhibitors in Patients With NSCLC Pretreated With Immune Checkpoint Inhibitors / Sisi, Monia; Vitale, Giovanni; Fusaroli, Michele; Riefolo, Mattia; Giunchi, Valentina; D’Errico, Antonietta; Ardizzoni, Andrea; Raschi, Emanuel; Gelsomino, Francesco. - In: JTO CLINICAL AND RESEARCH REPORTS. - ISSN 2666-3643. - ELETTRONICO. - 4:9(2023), pp. 100563.1-100563.8. [10.1016/j.jtocrr.2023.100563]
Sisi, Monia; Vitale, Giovanni; Fusaroli, Michele; Riefolo, Mattia; Giunchi, Valentina; D’Errico, Antonietta; Ardizzoni, Andrea; Raschi, Emanuel; Gelsomino, Francesco
File in questo prodotto:
File Dimensione Formato  
Sisi et al. JTO CCR 23.pdf

accesso aperto

Descrizione: Brief Report
Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale - Non opere derivate (CCBYNCND)
Dimensione 1.06 MB
Formato Adobe PDF
1.06 MB Adobe PDF Visualizza/Apri
Sisi et al. JTO CCR supplementary 23.pdf

accesso aperto

Descrizione: Supplementary Material
Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale - Non opere derivate (CCBYNCND)
Dimensione 29.79 kB
Formato Adobe PDF
29.79 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/957644
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 0
social impact