Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ adverse effects
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Drug-Related Side Effects and Adverse Reactions
/ epidemiology
Female
Humans
Immune System Diseases
/ epidemiology
Immunotherapy
/ adverse effects
Italy
/ epidemiology
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Nivolumab
/ adverse effects
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Retrospective Studies
Survival Analysis
Treatment Outcome
Young Adult
Immune-related adverse events
Immunotherapy
NSCLC
Nivolumab
Pembrolizumab
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
03
10
2018
revised:
19
12
2018
accepted:
13
02
2019
pubmed:
20
3
2019
medline:
4
4
2020
entrez:
20
3
2019
Statut:
ppublish
Résumé
Immune-related adverse events (irAEs) developed during immunotherapy with anti-PD-1 agents, could be a predictive surrogate marker of clinical benefit in patients with advanced non-small-cell lung cancer (NSCLC). Patients with NSCLC, treated with anti-PD-1 agents, were retrospectively evaluated. Univariate and multivariate analyses were performed to evaluate the relationships between types of irAEs (differentiated according to system/organ involved and to single-site/multiple-site), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). We further performed a 6-week landmark analysis. A total of 559 patients were enrolled; 231 patients (41.3%) developed irAEs of any grade and 50 patients (8.9%) G3/G4 events; 191 of them (82.6%) developed "single-site" irAEs and 40 (17.4%) "multiple-site" irAEs. At multivariate analysis, higher ORR was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), endocrine (P = .0043) and skin irAEs (P = .0005). Longer PFS was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), "multiple-site" irAEs (P = .0374), endocrine irAEs (P = .0084) and skin irAEs (P = .0001). Longer OS was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), endocrine irAEs (P = .0044), gastrointestinal irAEs (P = .0437), skin irAEs (P = .0006), and others irAEs (P = .0378). At the 6-week landmark analysis, irAEs of any grade was confirmed an independent predictor of higher ORR, longer PFS, and longer OS. Our study confirmed that irAEs are concordantly related to higher ORR, longer PFS, and longer OS with anti-PD-1 immunotherapy in patients with NSCLC.
Sections du résumé
BACKGROUND
Immune-related adverse events (irAEs) developed during immunotherapy with anti-PD-1 agents, could be a predictive surrogate marker of clinical benefit in patients with advanced non-small-cell lung cancer (NSCLC).
METHODS
Patients with NSCLC, treated with anti-PD-1 agents, were retrospectively evaluated. Univariate and multivariate analyses were performed to evaluate the relationships between types of irAEs (differentiated according to system/organ involved and to single-site/multiple-site), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). We further performed a 6-week landmark analysis.
RESULTS
A total of 559 patients were enrolled; 231 patients (41.3%) developed irAEs of any grade and 50 patients (8.9%) G3/G4 events; 191 of them (82.6%) developed "single-site" irAEs and 40 (17.4%) "multiple-site" irAEs. At multivariate analysis, higher ORR was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), endocrine (P = .0043) and skin irAEs (P = .0005). Longer PFS was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), "multiple-site" irAEs (P = .0374), endocrine irAEs (P = .0084) and skin irAEs (P = .0001). Longer OS was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), endocrine irAEs (P = .0044), gastrointestinal irAEs (P = .0437), skin irAEs (P = .0006), and others irAEs (P = .0378). At the 6-week landmark analysis, irAEs of any grade was confirmed an independent predictor of higher ORR, longer PFS, and longer OS.
CONCLUSION
Our study confirmed that irAEs are concordantly related to higher ORR, longer PFS, and longer OS with anti-PD-1 immunotherapy in patients with NSCLC.
Identifiants
pubmed: 30885550
pii: S1525-7304(19)30025-7
doi: 10.1016/j.cllc.2019.02.006
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Nivolumab
31YO63LBSN
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
237-247.e1Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.