Denis Maillet1, Pauline Corbaux2, Jean-Jacques Stelmes3, Stéphane Dalle4, Myriam Locatelli-Sanchez5, Marie Perier-Muzet4, Michaël Duruisseaux6, Lize Kiakouama-Maleka7, Gilles Freyer8, Amélie Boespflug4, Julien Péron9. 1. 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. 2. 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. 3. Department of Radiation Oncology, University Hospital Zurich, Switzerland. 4. 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; Hospices Civils de Lyon, Cancer Research Center of Lyon, Dermatology Department, Pierre-Bénite, France. 5. 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; Hospices Civils de Lyon, Cancer Research Center of Lyon, Department of Respiratory Medicine, Pierre-Bénite, France. 6. 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; Hospices Civils de Lyon, Department of Respiratory Medicine, Groupement Hospitalier Est, Hôpital Louis-Pradel, Lyon, France. 7. 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; Hospices Civils de Lyon, Department of Respiratory Medicine, Croix-rousse Hospital, Lyon, France. 8. Hospices Civils de Lyon, Oncology Department, Pierre-Bénite, France; Université de Lyon, F-69000 Lyon, France; Université Lyon 1, F-69100 Villeurbanne, France. 9. 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; CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, F-69100 Villeurbanne, France.
Abstract
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.
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.