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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.
- Source :
-
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2023 Oct; Vol. 18 (10), pp. 1408-1415. Date of Electronic Publication: 2023 May 20. - Publication Year :
- 2023
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Abstract
- 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.<br />Methods: This is a multicenter, retrospective study of consecutive advanced KRAS <superscript>G12C</superscript> -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.<br />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.<br />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.<br /> (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Proto-Oncogene Proteins p21(ras) therapeutic use
Retrospective Studies
Ligands
Cell Death
Lung Neoplasms drug therapy
Lung Neoplasms genetics
Lung Neoplasms chemically induced
Antineoplastic Agents, Immunological therapeutic use
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung chemically induced
Drug-Related Side Effects and Adverse Reactions
Chemical and Drug Induced Liver Injury etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1556-1380
- Volume :
- 18
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 37217096
- Full Text :
- https://doi.org/10.1016/j.jtho.2023.05.013