PMID- 37217096
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231027
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 18
IP  - 10
DP  - 2023 Oct
TI  - Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse 
      Events Associated With Sequential Anti-Programmed Cell Death (Ligand)1 and 
      Sotorasib Therapy in KRAS(G12C)-Mutant Lung Cancer.
PG  - 1408-1415
LID - S1556-0864(23)00572-5 [pii]
LID - 10.1016/j.jtho.2023.05.013 [doi]
AB  - INTRODUCTION: Sequential anti-programmed cell death protein 1 (PD-1) or 
      anti-programmed death-ligand 1 (PD-L1) followed by small targeted therapy use is 
      associated with increased prevalence of adverse events (AEs) in NSCLC. KRASG12C 
      inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used 
      in sequence or in combination with anti-PD-(L)1. This study was designed to 
      address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk 
      of hepatotoxicity and other AEs. METHODS: This is a multicenter, retrospective 
      study of consecutive advanced KRAS(G12C)-mutant NSCLC treated with sotorasib 
      outside clinical trials in 16 French medical centers. Patient records were 
      reviewed to identify sotorasib-related AEs (National Cancer Institute Common 
      Classification Criteria for Adverse Events-Version 5.0). Grade 3 and higher AE 
      was considered as severe. Sequence group was defined as patients who received an 
      anti-PD-(L)1 as last line of treatment before sotorasib initiation and control 
      group as patients who did not receive an anti-PD-(L)1 as last line of treatment 
      before sotorasib initiation. RESULTS: We identified 102 patients who received 
      sotorasib, including 48 (47%) in the sequence group and 54 (53%) in the control 
      group. Patients in the control group received an anti-PD-(L)1 followed by at 
      least one treatment regimen before sotorasib in 87% of the cases or did not 
      receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe 
      sotorasib-related AEs were significantly more frequent in the sequence group 
      compared with those in the control group (50% versus 13%, p < 0.001). Severe 
      sotorasib-related AEs occurred in 24 patients (24 of 48, 50%) in the sequence 
      group, and among them 16 (67%) experienced a severe sotorasib-related 
      hepatotoxicity. Severe sotorasib-related hepatotoxicity was threefold more 
      frequent in the sequence group compared with that in the control group (33% 
      versus 11%, p = 0.006). No fatal sotorasib-related hepatotoxicity was reported. 
      Non-liver severe sotorasib-related AEs were significantly more frequent in the 
      sequence group (27% versus 4%, p < 0.001). Severe sotorasib-related AEs typically 
      occurred in patients who received last anti-PD-(L)1 infusion within 30 days 
      before sotorasib initiation. CONCLUSIONS: Sequential anti-PD-(L)1 and sotorasib 
      therapy are associated with a significantly increased risk of severe 
      sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding 
      starting sotorasib within 30 days from the last anti-PD-(L)1 infusion.
CI  - Copyright (c) 2023 International Association for the Study of Lung Cancer. 
      Published by Elsevier Inc. All rights reserved.
FAU - Chour, Ali
AU  - Chour A
AD  - Respiratory Department and Early Phase, Louis Pradel Hospital, Hospices Civils de 
      Lyon Cancer Institute, Lyon, France; Oncopharmacology Laboratory, Cancer Research 
      Center of Lyon, Unite mixte de recherche (UMR) Institut national de la sante et 
      de la recherche medicale (INSERM) 1052 Centre national de la recherche 
      scientifique (CNRS) 5286, Lyon, France; Universite Claude Bernard, Universite de 
      Lyon, Lyon, France.
FAU - Denis, Julie
AU  - Denis J
AD  - Respiratory Department and Early Phase, Louis Pradel Hospital, Hospices Civils de 
      Lyon Cancer Institute, Lyon, France; Universite Claude Bernard, Universite de 
      Lyon, Lyon, France.
FAU - Mascaux, Celine
AU  - Mascaux C
AD  - Pulmonology Department, University Hospital of Strasbourg, Strasbourg, France; 
      Universite de Strasbourg, Institut national de la sante et de la recherche 
      medicale (INSERM) Unite mixte de recherche (UMR)_S 1113, IRFAC, Laboratory 
      Streinth (Stress REsponse and INnovative THerapy against cancer), ITI InnoVec, 
      Strasbourg, France.
FAU - Zysman, Maeva
AU  - Zysman M
AD  - Service des Maladies Respiratoires et des epreuves fonctionnelles respiratoires 
      CHU Bordeaux, Pessac, France; Univ-Bordeaux, Centre de Recherche 
      cardio-thoracique de Bordeaux, U1045, CIC 1401.-F, Pessac, France.
FAU - Bigay-Game, Laurence
AU  - Bigay-Game L
AD  - Unite d'oncologie Thoracique, Hopitaux de Toulouse, Toulouse, France.
FAU - Swalduz, Aurelie
AU  - Swalduz A
AD  - Centre Leon Berard, Lyon, France.
FAU - Gounant, Valerie
AU  - Gounant V
AD  - Thoracic Oncology Department-Early Phases Unit CIC-1425 Institut national de la 
      sante et de la recherche medicale (INSERM), Institut du cancer Assistance 
      Publique-Hopitaux de Paris (AP-HP) Nord, Hopital Bichat-Claude Bernard, Paris, 
      France; Universite Paris Cite, Paris, France.
FAU - Cortot, Alexis
AU  - Cortot A
AD  - Thoracic Oncology Department, Centre Hospitalier Regional Universitaire de Lille, 
      Lille, France.
FAU - Darrason, Marie
AU  - Darrason M
AD  - Service de Pneumologie, Lyon Sud Hospital Center, Pierre-Benite, France.
FAU - Fallet, Vincent
AU  - Fallet V
AD  - Hopital Tenon Assistance Publique-Hopitaux de Paris (AP-HP), Paris, France; GRC 
      4, Theranoscan, Sorbonne Universite, Paris, France.
FAU - Auclin, Edouard
AU  - Auclin E
AD  - Oncology Department, Hopital Europeen Georges Pompidou, Assistance 
      Publique-Hopitaux de Paris (AP-HP) centre, Universite Paris Cite, Paris, France.
FAU - Basse, Clemence
AU  - Basse C
AD  - Thorax Institute Curie Montsouris, Institut Curie, Paris, France; UVSQ, Paris 
      Saclay University, Versailles, France.
FAU - Tissot, Claire
AU  - Tissot C
AD  - Institut de Cancerologie de la Loire, Saint-Priest-en-Jarez, France.
FAU - Decroisette, Chantal
AU  - Decroisette C
AD  - Le Centre Hospitalier Annecy Genevois, Metz-Tessy, France.
FAU - Bombaron, Pierre
AU  - Bombaron P
AD  - Hopital Prive Jean Mermoz, Lyon, France.
FAU - Giroux-Leprieur, Etienne
AU  - Giroux-Leprieur E
AD  - Respiratory Diseases and Thoracic Oncology Department, Hopital Ambroise Pare 
      Assistance Publique-Hopitaux de Paris (AP-HP), Boulogne-Billancourt, France.
FAU - Odier, Luc
AU  - Odier L
AD  - Department of Pneumology, Hopital Nord-Ouest Villefranche, Villefranche Sur 
      Saone, France.
FAU - Brosseau, Solenn
AU  - Brosseau S
AD  - Thoracic Oncology Department-Early Phases Unit CIC-1425 Institut national de la 
      sante et de la recherche medicale (INSERM), Institut du cancer Assistance 
      Publique-Hopitaux de Paris (AP-HP) Nord, Hopital Bichat-Claude Bernard, Paris, 
      France; Universite Paris Cite, Paris, France.
FAU - Creusot, Quentin
AU  - Creusot Q
AD  - Pulmonology Department, University Hospital of Strasbourg, Strasbourg, France; 
      Universite de Strasbourg, Institut national de la sante et de la recherche 
      medicale (INSERM) Unite mixte de recherche (UMR)_S 1113, IRFAC, Laboratory 
      Streinth (Stress REsponse and INnovative THerapy against cancer), ITI InnoVec, 
      Strasbourg, France.
FAU - Guecamburu, Marina
AU  - Guecamburu M
AD  - Service des Maladies Respiratoires et des epreuves fonctionnelles respiratoires 
      CHU Bordeaux, Pessac, France; Univ-Bordeaux, Centre de Recherche 
      cardio-thoracique de Bordeaux, U1045, CIC 1401.-F, Pessac, France.
FAU - Meersseman, Corentin
AU  - Meersseman C
AD  - Centre Leon Berard, Lyon, France.
FAU - Rochand, Adrien
AU  - Rochand A
AD  - Oncology Department, Hopital Europeen Georges Pompidou, Assistance 
      Publique-Hopitaux de Paris (AP-HP) centre, Universite Paris Cite, Paris, France.
FAU - Costantini, Adrien
AU  - Costantini A
AD  - Respiratory Diseases and Thoracic Oncology Department, Hopital Ambroise Pare 
      Assistance Publique-Hopitaux de Paris (AP-HP), Boulogne-Billancourt, France.
FAU - Gaillard, Claire Marine
AU  - Gaillard CM
AD  - Department of Pneumology, Hopital Nord-Ouest Villefranche, Villefranche Sur 
      Saone, France.
FAU - Wasielewski, Eric
AU  - Wasielewski E
AD  - Thoracic Oncology Department, Centre Hospitalier Regional Universitaire de Lille, 
      Lille, France.
FAU - Girard, Nicolas
AU  - Girard N
AD  - Thorax Institute Curie Montsouris, Institut Curie, Paris, France; UVSQ, Paris 
      Saclay University, Versailles, France.
FAU - Cadranel, Jacques
AU  - Cadranel J
AD  - Hopital Tenon Assistance Publique-Hopitaux de Paris (AP-HP), Paris, France.
FAU - Lafitte, Claire
AU  - Lafitte C
AD  - Respiratory Department and Early Phase, Louis Pradel Hospital, Hospices Civils de 
      Lyon Cancer Institute, Lyon, France.
FAU - Lebosse, Fanny
AU  - Lebosse F
AD  - Hepatology unit, Croix Rousse hospital, Lyon Liver Institute, Hospices Civils of 
      Lyon, Lyon, France; Cancer Research Center of Lyon, Unite mixte de recherche 
      (UMR) Institut national de la sante et de la recherche medicale (INSERM) 1052 
      Centre national de la recherche scientifique (CNRS) 5286, Lyon, France.
FAU - Duruisseaux, Michael
AU  - Duruisseaux M
AD  - Respiratory Department and Early Phase, Louis Pradel Hospital, Hospices Civils de 
      Lyon Cancer Institute, Lyon, France; Oncopharmacology Laboratory, Cancer Research 
      Center of Lyon, Unite mixte de recherche (UMR) Institut national de la sante et 
      de la recherche medicale (INSERM) 1052 Centre national de la recherche 
      scientifique (CNRS) 5286, Lyon, France; Universite Claude Bernard, Universite de 
      Lyon, Lyon, France. Electronic address: michael.duruisseaux@chu-lyon.fr.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20230520
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 2B2VM6UC8G (sotorasib)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - 0 (Ligands)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (KRAS protein, human)
SB  - IM
CIN - J Thorac Oncol. 2023 Oct;18(10):e112-e113. PMID: 37758348
CIN - J Thorac Oncol. 2023 Oct;18(10):e114-e115. PMID: 37758349
MH  - Humans
MH  - *Lung Neoplasms/drug therapy/genetics/chemically induced
MH  - Proto-Oncogene Proteins p21(ras)/therapeutic use
MH  - Retrospective Studies
MH  - Ligands
MH  - *Antineoplastic Agents, Immunological/therapeutic use
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/chemically induced
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - *Chemical and Drug Induced Liver Injury/etiology
MH  - Cell Death
OTO - NOTNLM
OT  - Anti-PD-(L)1
OT  - Hepatotoxicity
OT  - KRAS(G12C) mutation
OT  - Non-small cell lung cancer
OT  - Sequence
OT  - Sotorasib
EDAT- 2023/05/23 01:06
MHDA- 2023/10/23 12:46
CRDT- 2023/05/22 19:21
PHST- 2023/02/12 00:00 [received]
PHST- 2023/04/28 00:00 [revised]
PHST- 2023/05/15 00:00 [accepted]
PHST- 2023/10/23 12:46 [medline]
PHST- 2023/05/23 01:06 [pubmed]
PHST- 2023/05/22 19:21 [entrez]
AID - S1556-0864(23)00572-5 [pii]
AID - 10.1016/j.jtho.2023.05.013 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2023 Oct;18(10):1408-1415. doi: 10.1016/j.jtho.2023.05.013. Epub 
      2023 May 20.