Age favoured overall survival in a large population-based Danish patient cohort treated with anti-PD1 immune checkpoint inhibitor for metastatic melanoma.
Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antineoplastic Agents, Immunological
/ therapeutic use
CTLA-4 Antigen
/ antagonists & inhibitors
Child, Preschool
Cohort Studies
Denmark
Female
Humans
Ipilimumab
/ therapeutic use
Male
Melanoma
/ drug therapy
Middle Aged
Neoplasm Metastasis
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Skin Neoplasms
/ drug therapy
Survival Analysis
Age
Anti-CTLA4
Anti-PD1
Antibodies
Ipilimumab
Malignant melanoma
Monoclonal
Pembrolizumab
Survival
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
20
12
2018
revised:
04
06
2019
accepted:
28
06
2019
pubmed:
24
8
2019
medline:
9
6
2020
entrez:
24
8
2019
Statut:
ppublish
Résumé
Age-related immune dysfunction (ARID) describes age-associated changes in immunity that may affect the efficacy of immunotherapy with checkpoint inhibitors. We evaluated the efficacy of treatment with ipilimumab (530 patients) or pembrolizumab (562 patients) in a Danish national cohort of metastatic melanoma patients. We confirmed known prognostic biomarkers related to treatment with ipilimumab and found no impact of age on survival or progression-free survival. In patients treated with pembrolizumab, we also confirmed known prognostic biomarkers. Overall survival (OS) and progression-free survival was significantly higher in patients aged between 70 and 80 years compared with younger patients. In multivariate analysis with OS as end-point, age was shown to be an independent good prognostic biomarker in these patients. Survival in patients aged above 80 years was not better than in younger patients, probably because of increase in significant comorbidity. Our analyses have revealed a higher survival rate when using drugs targeting PD1 in metastatic melanoma patients between the age of 70 and 80 years. ARID does not seem to negatively impact the efficacy of treatment with checkpoint inhibitors in metastatic melanoma patients. Despite these encouraging data for elderly patients, clinicians still need to carefully consider the higher risk of more serious outcomes of the immune-related adverse events in the elderly patient population, before deciding to treat old patients with checkpoint inhibitors.
Sections du résumé
BACKGROUND AND PATIENTS
Age-related immune dysfunction (ARID) describes age-associated changes in immunity that may affect the efficacy of immunotherapy with checkpoint inhibitors. We evaluated the efficacy of treatment with ipilimumab (530 patients) or pembrolizumab (562 patients) in a Danish national cohort of metastatic melanoma patients.
RESULTS
We confirmed known prognostic biomarkers related to treatment with ipilimumab and found no impact of age on survival or progression-free survival. In patients treated with pembrolizumab, we also confirmed known prognostic biomarkers. Overall survival (OS) and progression-free survival was significantly higher in patients aged between 70 and 80 years compared with younger patients. In multivariate analysis with OS as end-point, age was shown to be an independent good prognostic biomarker in these patients. Survival in patients aged above 80 years was not better than in younger patients, probably because of increase in significant comorbidity.
CONCLUSIONS
Our analyses have revealed a higher survival rate when using drugs targeting PD1 in metastatic melanoma patients between the age of 70 and 80 years. ARID does not seem to negatively impact the efficacy of treatment with checkpoint inhibitors in metastatic melanoma patients. Despite these encouraging data for elderly patients, clinicians still need to carefully consider the higher risk of more serious outcomes of the immune-related adverse events in the elderly patient population, before deciding to treat old patients with checkpoint inhibitors.
Identifiants
pubmed: 31442816
pii: S0959-8049(19)30414-9
doi: 10.1016/j.ejca.2019.06.022
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
CTLA-4 Antigen
0
Ipilimumab
0
Programmed Cell Death 1 Receptor
0
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
122-131Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.