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Management of sotorasib-related adverse events and hepatotoxicities following anti-PD-(L)1 therapy: Experience with sotorasib in two French anti-cancer centers and practical guidance proposal.
- Source :
-
Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2024 May; Vol. 191, pp. 107789. Date of Electronic Publication: 2024 Apr 09. - Publication Year :
- 2024
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Abstract
- Introduction: Sotorasib is a first-in-class KRASG12C inhibitor that showed significant clinical activity in KRAS <superscript>G12C</superscript> -mutated non-small cell lung cancer (NSCLC). The most frequent grade 3 or 4 sotorasib-related adverse events (AEs) were diarrhea (4-12 %) and hepatotoxicity (10.1-15.1 %). Data is lacking about the management of these AEs, especially in patients receiving sequential anti-PD-(L)1 and sotorasib therapy. Our aim was to report the management of grade ≥ 2 sotorasib-related AEs in real-world setting and to propose practical guidance for the management of grade ≥ 2 sotorasib-related AEs and more generally KRASG12C inhibitors-related AEs.<br />Materials and Methods: Records from all consecutive patients who initiated sotorasib through expanded access program in two French anti-cancer centers from January 1st 2021 to April 1st 2023 were reviewed to identify and grade sotorasib-related AEs, according to NCI-CTCAE v5.0., and to collect AEs management data. Patients were included in the analysis if they presented a grade ≥ 2 sotorasib-related AE.<br />Results: From 57 patients identified, 21 met inclusion criteria including eighteen (86 %) who received sequential anti-PD-(L)1 and sotorasib therapy. Hepatotoxicity (76 %) and diarrhea (24 %) were the most common grade ≥ 2 sotorasib-related AEs. Among the 16 patients with a grade ≥ 2 hepatotoxicity, 12 (75 %) definitely discontinued sotorasib, among which 9 (56 %) after dose reductions and rechallenge, and five (32 %) received corticosteroids, allowing only one patient to resume sotorasib. Diarrhea and nausea were usually manageable and not associated with sotorasib discontinuation. We propose a step-by-step management practical guidance for sotorasib-related hepatotoxicity based on dose-reduction and careful monitoring. Liver biopsy is strongly encouraged for grade 3 and 4 hepatotoxicity to assess candidates for corticosteroids.<br />Discussion: The experience with sotorasib might help better prevent, screen and manage sotorasib-related and other KRASG12C inhibitors-related AEs, particularly hepatotoxicity.<br />Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Ali Chour (ali.chour@chu-lyon.fr) reported no disclosures. Clémence Basse (clemence.basse@curie.fr) reported no disclosures. Nicolas Girard (nicolas.girard2@curie.fr) reported research grants/support from AstraZeneca, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Sivan, and Trizell; consultative services for Bristol Myers Squibb, AstraZeneca, AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, Merck Sharp & Dohme, Mirati, Novartis, Pfizer, Roche, Sanofi, and Sivan; payment for expert testimony from AstraZeneca; participation on a data safety monitoring board for Roche; leadership role in the International Thymic Malignancy Interest Group; and having employment of a family member with AstraZeneca. Fanny Lebossé (fanny.lebosse@chu-lyon.fr) reported no disclosures. Pierre-Emmanuel Bonté (pierreemmanuel.bonte@curie.fr) reported no disclosures. Michael Duruisseaux (michael.duruisseaux@chu-lyon.fr) reported Membership of an advisory council or committee for BMS, GSK, Sanofi, MSD, AstraZeneca, Abbvie, Takeda, Boehringer Ingelheim, Merus, Amgen, Guardant, Pfizer; consulting fees from Roche, BMS, MSD, AstraZeneca, AbbVie, Takeda, Boehringer Ingelheim, Gamamabs Pharma, Pfizer; research grants from Takeda, NanoString, Lilly, Blueprint.].<br /> (Copyright © 2024. Published by Elsevier B.V.)
- Subjects :
- Humans
Male
Female
Aged
Middle Aged
France
Immune Checkpoint Inhibitors adverse effects
Immune Checkpoint Inhibitors therapeutic use
Aged, 80 and over
Pyridines therapeutic use
Pyridines adverse effects
Retrospective Studies
Adult
Pyrimidines therapeutic use
Pyrimidines adverse effects
Drug-Related Side Effects and Adverse Reactions etiology
Diarrhea chemically induced
B7-H1 Antigen antagonists & inhibitors
Disease Management
Practice Guidelines as Topic
Chemical and Drug Induced Liver Injury etiology
Carcinoma, Non-Small-Cell Lung drug therapy
Lung Neoplasms drug therapy
Piperazines
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8332
- Volume :
- 191
- Database :
- MEDLINE
- Journal :
- Lung cancer (Amsterdam, Netherlands)
- Publication Type :
- Academic Journal
- Accession number :
- 38614068
- Full Text :
- https://doi.org/10.1016/j.lungcan.2024.107789