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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.
Chour, Ali; Basse, Clémence; Lebossé, Fanny; Bonte, Pierre-Emmanuel; Girard, Nicolas; Duruisseaux, Michaël.
Affiliation
  • Chour A; Respiratory Department and Early Phase (EPSILYON), Louis Pradel Hospital, Hospices Civils de Lyon Cancer Institute, Lyon, France; Oncopharmacology Laboratory, Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Lyon, France; Université Claude Bernard, Université de Lyon, Lyon, France.
  • Basse C; Thoracic Oncology, Institut du Thorax Curie Montsouris, Hôpital Institute Curie Paris-St Cloud; University of Versailles Saint Quentin, Faculté de médecine Simone-Veil, Paris Saclay University, Versailles, France.
  • Lebossé F; Hepatology unit, Croix-Rousse Hospital, Lyon Liver Institute, Hospices Civils de Lyon, Lyon, France; Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Lyon, France.
  • Bonte PE; Institut Curie, PSL University, Inserm U932, Immunity and Cancer, 75005 Paris, France.
  • Girard N; Thoracic Oncology, Institut du Thorax Curie Montsouris, Hôpital Institute Curie Paris-St Cloud; University of Versailles Saint Quentin, Faculté de médecine Simone-Veil, Paris Saclay University, Versailles, France.
  • Duruisseaux M; Respiratory Department and Early Phase (EPSILYON), Louis Pradel Hospital, Hospices Civils de Lyon Cancer Institute, Lyon, France; Oncopharmacology Laboratory, Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Lyon, France; Université Claude Bernard, Université de Lyon, Lyon, France. Electro
Lung Cancer ; 191: 107789, 2024 May.
Article in 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 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.

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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Piperazines / Carcinoma, Non-Small-Cell Lung / Chemical and Drug Induced Liver Injury / Lung Neoplasms Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: En Journal: Lung Cancer Journal subject: NEOPLASIAS Year: 2024 Type: Article Affiliation country: France

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Piperazines / Carcinoma, Non-Small-Cell Lung / Chemical and Drug Induced Liver Injury / Lung Neoplasms Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: En Journal: Lung Cancer Journal subject: NEOPLASIAS Year: 2024 Type: Article Affiliation country: France