Association Between Immune-related Adverse Events and Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer.


Journal

Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225

Informations de publication

Date de publication:
05 2019
Historique:
received: 11 05 2018
revised: 21 09 2018
accepted: 03 10 2018
pubmed: 18 11 2018
medline: 4 4 2020
entrez: 17 11 2018
Statut: ppublish

Résumé

Immune checkpoint inhibitors (ICIs) are available for first- and further lines of treatment of patients with advanced non-small-cell lung cancer (NSCLC). These treatments are associated with adverse events called immune-related adverse events (IRAEs). The incidence, diagnosis, and treatment of IRAEs are quite acknowledged; however, the link between IRAEs and the efficacy of ICIs requires further clarification. The objectives of this study were to assess the association between IRAEs incidence and severity and ICIs efficacy in patients with advanced NSCLC. In this retrospective study, clinical, biological, treatment, and outcome data were collected from patients with advanced NSCLC who received at least 1 cycle of ICIs from April 2013 to February 2017. The primary endpoint was to assess the association of IRAEs incidence with overall survival (OS). Secondary endpoints were the association of IRAEs with progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Overall, 270 patients were studied. The median OS was 14 months, median PFS was 2.6 months, ORR was 13%, and DCR was 51%. OS, PFS, and ORR were significantly better for patients with IRAEs compared with patients with no IRAEs, translating to median OS not reached versus 8.21 months, respectively (hazard ratio, 0.29; 95% confidence interval [CI], 0.18-0.46; P < .001); PFS was 5.2 versus 1.97 months (hazard ratio, 0.42; 95% CI, 0.32-0.57; P < .001); and ORR was 212.9% versus 5.7% (odds ratio, 4.9; 95% CI, 2.18-11.05; P < .001). This report presents the largest case series showing longer OS and PFS and better ORR when IRAEs occurred in a population of patients with advanced NSCLC treated with ICIs. The biological background for this phenomenon is being explored prospectively.

Sections du résumé

BACKGROUND
Immune checkpoint inhibitors (ICIs) are available for first- and further lines of treatment of patients with advanced non-small-cell lung cancer (NSCLC). These treatments are associated with adverse events called immune-related adverse events (IRAEs). The incidence, diagnosis, and treatment of IRAEs are quite acknowledged; however, the link between IRAEs and the efficacy of ICIs requires further clarification. The objectives of this study were to assess the association between IRAEs incidence and severity and ICIs efficacy in patients with advanced NSCLC.
METHODS
In this retrospective study, clinical, biological, treatment, and outcome data were collected from patients with advanced NSCLC who received at least 1 cycle of ICIs from April 2013 to February 2017. The primary endpoint was to assess the association of IRAEs incidence with overall survival (OS). Secondary endpoints were the association of IRAEs with progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).
RESULTS
Overall, 270 patients were studied. The median OS was 14 months, median PFS was 2.6 months, ORR was 13%, and DCR was 51%. OS, PFS, and ORR were significantly better for patients with IRAEs compared with patients with no IRAEs, translating to median OS not reached versus 8.21 months, respectively (hazard ratio, 0.29; 95% confidence interval [CI], 0.18-0.46; P < .001); PFS was 5.2 versus 1.97 months (hazard ratio, 0.42; 95% CI, 0.32-0.57; P < .001); and ORR was 212.9% versus 5.7% (odds ratio, 4.9; 95% CI, 2.18-11.05; P < .001).
CONCLUSIONS
This report presents the largest case series showing longer OS and PFS and better ORR when IRAEs occurred in a population of patients with advanced NSCLC treated with ICIs. The biological background for this phenomenon is being explored prospectively.

Identifiants

pubmed: 30442524
pii: S1525-7304(18)30263-8
doi: 10.1016/j.cllc.2018.10.002
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antineoplastic Agents, Immunological 0
Costimulatory and Inhibitory T-Cell Receptors 0
Nivolumab 31YO63LBSN

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

201-207

Informations de copyright

Copyright © 2018 Elsevier Inc. All rights reserved.

Auteurs

Mathieu Grangeon (M)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Pascale Tomasini (P)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France; Aix Marseille University, Inserm U911 CRO2, Marseille, France. Electronic address: pascale.tomasini@ap-hm.fr.

Solene Chaleat (S)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Arnaud Jeanson (A)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Maxime Souquet-Bressand (M)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Nataliya Khobta (N)

Oncology Department, Centre Hospitalier Departemental de Castellccio, Ajaccio, France.

Julien Bermudez (J)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Youssef Trigui (Y)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Laurent Greillier (L)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France; Aix Marseille University, Inserm U911 CRO2, Marseille, France.

Marilyne Blanchon (M)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France.

Mohamed Boucekine (M)

Chronic Diseases and Quality of Life -Research Unit, Aix Marseille University, EA 3279 - Public Health, Marseille, France.

Celine Mascaux (C)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France; Aix Marseille University, Inserm U911 CRO2, Marseille, France.

Fabrice Barlesi (F)

Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France; Aix Marseille University, Inserm U911 CRO2, Marseille, France.

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Classifications MeSH