• Eur. J. Cancer · Jun 2020

    Association between immune-related adverse events and long-term survival outcomes in patients treated with immune checkpoint inhibitors.

    • Denis Maillet, Pauline Corbaux, Jean-Jacques Stelmes, Stéphane Dalle, Myriam Locatelli-Sanchez, Marie Perier-Muzet, Michaël Duruisseaux, Lize Kiakouama-Maleka, Gilles Freyer, Amélie Boespflug, and Julien Péron.
    • Hospices Civils de Lyon, Oncology Department, Pierre-Bénite, France; Université de Lyon, F-69000 Lyon, France; Université Lyon 1, F-69100 Villeurbanne, France; ImmuCare (Immunology Cancer Research) Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France. Electronic address: denis.maillet@chu-lyon.fr.
    • Eur. J. Cancer. 2020 Jun 1; 132: 61-70.

    BackgroundThe impact of immune-related adverse events (irAE) on survival outcomes after single-agent immune checkpoint inhibitors (ICIs) remains unclear. We aimed to evaluate the association between irAEs and ICI efficacy in various malignancies.MethodsAll patients treated with a single-agent ICI for any advanced cancer were included in this retrospective multicentric series. The primary objective was to assess the impact of all type grade ≥II irAEs on progression-free survival (PFS) and overall survival (OS). IrAEs were first considered as a fixed covariate and included in Cox-regression models. In addition, as irAEs are time-related events and can occur at any point during follow-up, we analysed the occurrence of irAEs as a time-varying covariate.ResultsIn this cohort of 410 patients, the majority of patients (70%) were treated for non-small cell lung cancer. The ICI was an anti-PD(L)1 for 356 patients (82%) and an anti-CTLA4 for 79 patients (18%). In total 126 (29%) of the patients presented at least one grade ≥II irAEs. The first occurrence of a grade ≥II irAE had a positive impact on PFS and OS when considered as a fixed or as a time-varying covariate (hazard ratio [HR] for PFS = 0.63, 95% confidence interval [CI] 0.50-0.81; P = 0.00022; HR for OS = 0.57, 95% CI 0.43-0.74, P < 0.0001). This overall finding was confirmed in patients treated with an anti-PD(L)1 and among patients with lung cancer.ConclusionIn this pooled multi-institutional cohort, the incidence of irAEs was associated with better long-term survival across different malignancies treated with ICI monotherapy.Copyright © 2020 Elsevier Ltd. All rights reserved.

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