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

Background: The 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. Methods: All patients treated with a single-agent I...

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Vydáno v:European journal of cancer (1990) Ročník 132; s. 61 - 70
Hlavní autoři: Maillet, Denis, Corbaux, Pauline, Stelmes, Jean-Jacques, Dalle, Stéphane, Locatelli-Sanchez, Myriam, Perier-Muzet, Marie, Duruisseaux, Michaël, Kiakouama-Maleka, Lize, Freyer, Gilles, Boespflug, Amélie, Péron, Julien
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Elsevier Ltd 01.06.2020
Elsevier Science Ltd
Elsevier
Témata:
Cancer
Confidence intervals
CTLA-4 protein
CTLA4 inhibitors
Immune checkpoint inhibitors
Immune-related adverse events
Inhibitors
Life Sciences
Lung cancer
Non-small cell lung carcinoma
PD1 inhibitors
PDL1 inhibitors
Prognostic biomarkers
Regression analysis
Regression models
Small cell lung carcinoma
Solid tumours
Statistical analysis
Survival
Survival analysis
PD1 inhibitors
PDL1 inhibitors
Prognostic biomarkers
Survival analysis
Immune-related adverse events
Solid tumours
CTLA4 inhibitors
Immune checkpoint inhibitors
ISSN:0959-8049, 1879-0852, 1879-0852
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Shrnutí:Background: The 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. Methods: All 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. Results: In 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. Conclusion: In this pooled multi-institutional cohort, the incidence of irAEs was associated with better long-term survival across different malignancies treated with ICI monotherapy. •Incidence of immune-related adverse events (irAEs) has a positive impact on progression-free survival and overall survival.•This overall finding was confirmed in patients treated with an anti-PD(L)1.•These results were confirmed when irAEs were considered as a time-varying covariate.
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ISSN:0959-8049
1879-0852
1879-0852
DOI:10.1016/j.ejca.2020.03.017