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.
Lung Cancer
; 191: 107789, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38614068
ABSTRACT
INTRODUCTION:
Sotorasib is a first-in-class KRASG12C inhibitor that showed significant clinical activity in KRASG12C-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. MATERIALS ANDMETHODS:
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.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.DISCUSSION:
The experience with sotorasib might help better prevent, screen and manage sotorasib-related and other KRASG12C inhibitors-related AEs, particularly hepatotoxicity.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Piperazinas
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Carcinoma Pulmonar de Células não Pequenas
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Doença Hepática Induzida por Substâncias e Drogas
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Neoplasias Pulmonares
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França