Time to next treatment or death as a candidate surrogate endpoint for overall survival in advanced melanoma patients treated with immune checkpoint inhibitors: an insight from the phase III CheckMate 067 trial.
advanced melanoma
immune checkpoint inhibitors
ipilimumab
nivolumab
overall survival
surrogate endpoint
time to next treatment
Journal
ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
19
03
2021
revised:
22
10
2021
accepted:
16
11
2021
pubmed:
21
12
2021
medline:
25
3
2022
entrez:
20
12
2021
Statut:
ppublish
Résumé
Time to next treatment or death (TNT-D) may be a patient-relevant endpoint in patients treated with immune checkpoint inhibitors. This study investigated TNT-D as a surrogate endpoint (SE) for overall survival (OS) in previously untreated advanced melanoma patients. Patient-level data from the 60-month results of the CheckMate 067 randomised, controlled trial were used. Analyses were carried out for nivolumab monotherapy or nivolumab with ipilimumab versus ipilimumab monotherapy. The SE 1-step validation method based on a joint frailty-copula model was used where the country of enrolment was applied to define clusters. Kendall's τ and the coefficient of determination (R Fifteen clusters of data were generated from 945 patients. For both nivolumab-containing arms, the association between TNT-D and OS was deemed acceptable at the individual level (Kendall's τ > 0.60) and strong at the cluster level, with R Results suggest that TNT-D may be a valuable SE in previously untreated advanced melanoma patients treated with immune checkpoint inhibitors. Surrogacy analyses considering multiple randomised controlled trials are warranted for confirming these findings.
Sections du résumé
BACKGROUND
Time to next treatment or death (TNT-D) may be a patient-relevant endpoint in patients treated with immune checkpoint inhibitors. This study investigated TNT-D as a surrogate endpoint (SE) for overall survival (OS) in previously untreated advanced melanoma patients.
METHODS
Patient-level data from the 60-month results of the CheckMate 067 randomised, controlled trial were used. Analyses were carried out for nivolumab monotherapy or nivolumab with ipilimumab versus ipilimumab monotherapy. The SE 1-step validation method based on a joint frailty-copula model was used where the country of enrolment was applied to define clusters. Kendall's τ and the coefficient of determination (R
RESULTS
Fifteen clusters of data were generated from 945 patients. For both nivolumab-containing arms, the association between TNT-D and OS was deemed acceptable at the individual level (Kendall's τ > 0.60) and strong at the cluster level, with R
CONCLUSION
Results suggest that TNT-D may be a valuable SE in previously untreated advanced melanoma patients treated with immune checkpoint inhibitors. Surrogacy analyses considering multiple randomised controlled trials are warranted for confirming these findings.
Identifiants
pubmed: 34929616
pii: S2059-7029(21)00302-1
doi: 10.1016/j.esmoop.2021.100340
pmc: PMC8693416
pii:
doi:
Substances chimiques
Biomarkers
0
Immune Checkpoint Inhibitors
0
Ipilimumab
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100340Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure SB, A-FG, MK and AM are employed by Bristol Myers Squibb (BMS). CLS and VR declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. AI declares advisory board consulting with Epizyme, Lilly, Merck Sharp & Dohme, Novartis, Pharmamar and Roche; and research grants from AstraZeneca, Bayer, BMS, Chugai, Merck Sharp & Dohme, Novartis, Pharmamar, Pfizer and Roche. CB declares personal fees from BMS outside of the submitted work.