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

Humans Lung Neoplasms / drug therapy Proto-Oncogene Proteins p21(ras) / therapeutic use Retrospective Studies Ligands Antineoplastic Agents, Immunological / therapeutic use Carcinoma, Non-Small-Cell Lung / drug therapy Drug-Related Side Effects and Adverse Reactions Chemical and Drug Induced Liver Injury / etiology Cell Death

Anti–PD-(L)1 Hepatotoxicity KRAS(G12C) mutation Non–small cell lung cancer Sequence Sotorasib

Journal

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

ISSN: 1556-1380

Titre abrégé: J Thorac Oncol

Pays: United States

ID NLM: 101274235

Informations de publication

Date de publication:
10 2023

Historique:

received: 12 02 2023

revised: 28 04 2023

accepted: 15 05 2023

medline: 23 10 2023

pubmed: 23 5 2023

entrez: 22 5 2023

Statut: ppublish

Résumé

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. This is a multicenter, retrospective study of consecutive advanced KRAS 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. 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.

Identifiants

DOI: 10.1016/j.jtho.2023.05.013 PMID: 37217096

pubmed: 37217096

pii: S1556-0864(23)00572-5

doi: 10.1016/j.jtho.2023.05.013

pii:

doi:

Substances chimiques

sotorasib 2B2VM6UC8G

Proto-Oncogene Proteins p21(ras) EC 3.6.5.2

Ligands 0

Antineoplastic Agents, Immunological 0

KRAS protein, human 0

Types de publication

Multicenter Study Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1408-1415

Commentaires et corrections

Type : CommentIn