The Pan-Immune-Inflammation Value in microsatellite instability-high metastatic colorectal cancer patients treated with immune checkpoint inhibitors.
Aged
Blood Platelets
/ immunology
Colorectal Neoplasms
/ drug therapy
Female
Genetic Predisposition to Disease
Humans
Immune Checkpoint Inhibitors
/ adverse effects
Inflammation
/ immunology
Lymphocytes, Tumor-Infiltrating
/ immunology
Male
Microsatellite Instability
Monocytes
/ immunology
Neoplasm Metastasis
Neutrophils
/ immunology
Phenotype
Progression-Free Survival
Retrospective Studies
Time Factors
Tumor Microenvironment
/ immunology
Biomarkers
Colorectal cancer
Deficient mismatch repair
Immune checkpoint inhibitors
Microsatellite instability
Pan-Immune-Inflammation Value
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:
06 2021
06 2021
Historique:
received:
02
02
2021
revised:
10
03
2021
accepted:
18
03
2021
pubmed:
27
4
2021
medline:
26
10
2021
entrez:
26
4
2021
Statut:
ppublish
Résumé
Immune checkpoint inhibitors (ICIs) yielded unprecedented efficacy in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC). Since the Pan-Immune-Inflammation Value (PIV) is a blood-based biomarker with prognostic usefulness in mCRC, it might predict clinical outcomes and primary resistance to ICIs. We retrospectively analysed the association of PIV and its early modulation at 3/4 weeks after treatment initiation with the outcomes of MSI-high mCRC patients receiving anti-programmed death-(ligand)1 (PD-[L]1) +/- anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. PIV cut-offs were determined using the maximally selected rank statistics. A total of 163 patients were included. In the multivariable models for overall survival (OS) and progression-free survival (PFS), both high (>492) baseline PIV (OS: adjusted [a] HR, 3.00; 95% CI, 1.49-6.04, p = 0.002; PFS: aHR, 1.91; 95% CI, 1.06-3.44, p = 0.031) and early PIV increase ≥+30% (OS: aHR, 3.21; 95% CI, 1.65-6.23, p < 0.001; PFS: aHR, 2.25; 95% CI, 1.30-3.89, p = 0.003) confirmed an independent prognostic impact. After stratifying patients according to baseline PIV and ICI regimen, OS and PFS were significantly worse in subjects with high PIV receiving anti-PD-1/PD-L1 monotherapy. Early PIV increase was an independent predictor of clinical benefit (aOR, 0.23; 95% CI, 0.08-0.66; p = 0.007), whereas a trend was observed for baseline PIV (aOR, 0.33; 95% CI, 0.10-1.07; p = 0.065). PIV is a strong predictor of outcomes in MSI-high mCRC patients receiving ICIs. Prospective validation of these results is required to establish its role as a stratification factor for personalised combination strategies.
Sections du résumé
BACKGROUND
Immune checkpoint inhibitors (ICIs) yielded unprecedented efficacy in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC). Since the Pan-Immune-Inflammation Value (PIV) is a blood-based biomarker with prognostic usefulness in mCRC, it might predict clinical outcomes and primary resistance to ICIs.
METHODS
We retrospectively analysed the association of PIV and its early modulation at 3/4 weeks after treatment initiation with the outcomes of MSI-high mCRC patients receiving anti-programmed death-(ligand)1 (PD-[L]1) +/- anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. PIV cut-offs were determined using the maximally selected rank statistics.
RESULTS
A total of 163 patients were included. In the multivariable models for overall survival (OS) and progression-free survival (PFS), both high (>492) baseline PIV (OS: adjusted [a] HR, 3.00; 95% CI, 1.49-6.04, p = 0.002; PFS: aHR, 1.91; 95% CI, 1.06-3.44, p = 0.031) and early PIV increase ≥+30% (OS: aHR, 3.21; 95% CI, 1.65-6.23, p < 0.001; PFS: aHR, 2.25; 95% CI, 1.30-3.89, p = 0.003) confirmed an independent prognostic impact. After stratifying patients according to baseline PIV and ICI regimen, OS and PFS were significantly worse in subjects with high PIV receiving anti-PD-1/PD-L1 monotherapy. Early PIV increase was an independent predictor of clinical benefit (aOR, 0.23; 95% CI, 0.08-0.66; p = 0.007), whereas a trend was observed for baseline PIV (aOR, 0.33; 95% CI, 0.10-1.07; p = 0.065).
CONCLUSION
PIV is a strong predictor of outcomes in MSI-high mCRC patients receiving ICIs. Prospective validation of these results is required to establish its role as a stratification factor for personalised combination strategies.
Identifiants
pubmed: 33901794
pii: S0959-8049(21)00210-0
doi: 10.1016/j.ejca.2021.03.043
pii:
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
155-167Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement Sara Lonardi received honoraria for advisory boards/speakers bureau from Amgen, Merck Serono, Eli Lilly & Co, Roche, Eli Lilly & Co, Bristol-Myers Squibb, Servier and Merck Serono, and research funding from Amgen and Merck Serono. Matteo Fassan received research grants from Astellas Pharma e QED Therapeutics and honoraria for advisory boards from Astellas Pharma, Diaceutics and Tesaro. Federica Morano received honoraria from Servier. Giuseppe Curigliano received grants from Merck and honoraria for advisory boards from Merck, BMS, Novartis, Lilly, Pfizer, Astra Zeneca, Daichii Sankyo, Ellipsis and Seattle Genetics. Filippo de Braud received honoraria for advisory boards/speakers bureau from Ignyta, Pfizer, Amgen, Novartis, Daiichi Sankyo, Bristol-Myers Squibb, Dompè, PierreFabre, Roche, Octimet, Incyte, Teofarma, EMD Serono, MerckSharp & Dohme, Novartis, Bristol-Myers Squibb, Roche, Pfizer and Menarini, and research funding from Novartis, Roche, Merck Sharp & Dohme, Ignyta, MedImmune, Nektar, Bristol-Myers Squibb, MerckSerono, Bayer, Celgene, GlaxoSmithKline, Boehringer Ingelheim, EliLilly & Co, Pfizer and Servier. Filippo Pietrantonio received honoraria for speakers bureau from Servier, research grants from BMS and honoraria for advisory boards/speakers bureau from Roche, Amgen, Merck-Serono, Lilly, Sanofi, Bayer and Servier. The remaining authors declare no conflict of interest.