Tumor Mutational Burden, Toxicity, and Response of Immune Checkpoint Inhibitors Targeting PD(L)1, CTLA-4, and Combination: A Meta-regression Analysis.
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
B7-H1 Antigen
/ antagonists & inhibitors
Biomarkers, Tumor
/ genetics
CTLA-4 Antigen
/ antagonists & inhibitors
Clinical Trials as Topic
Drug-Related Side Effects and Adverse Reactions
/ diagnosis
Genetic Predisposition to Disease
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Mutation
Neoplasms
/ drug therapy
Regression Analysis
Risk Assessment
/ statistics & numerical data
Risk Factors
Severity of Illness Index
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 09 2020
15 09 2020
Historique:
received:
04
02
2020
revised:
25
04
2020
accepted:
18
06
2020
pubmed:
27
6
2020
medline:
15
12
2021
entrez:
27
6
2020
Statut:
ppublish
Résumé
Tumor mutational burden (TMB) has emerged as a potential predictive biomarker for clinical response to ICI therapy, but whether TMB also predicts toxicity remains unknown. We investigated the relationship between TMB, objective response rate (ORR), overall survival (OS), and toxicity for ICI therapy across multiple cancer types. We searched MEDLINE, PubMed, and ASCO/ESMO/AACR meetings for clinical trials of anti-PD(L)1, CTLA-4, or combination in 29 cancer types. We assessed ICI administered, responses (complete or partial response), median OS, OS HR, and grade 3/4 toxicity. We conducted a systematic review, meta-analysis and meta-regression using tumor level TMB data from Foundation Medicine. One hundred seventeen clinical trials, which included 12,450 patients treated with ICI therapy were analyzed. Meta-regression analysis revealed that TMB was significantly associated with ORR for anti-PD(L)1, anti-CTLA-4, and combination ( There is a positive association between TMB and clinical response with anti-PD(L)1, anti-CTLA-4, and combination ICIs, but no association between TMB and toxicity. These results imply a favorable risk/benefit ratio for ICIs in tumors with a higher TMB.
Identifiants
pubmed: 32586938
pii: 1078-0432.CCR-20-0458
doi: 10.1158/1078-0432.CCR-20-0458
pmc: PMC7501151
mid: NIHMS1607188
doi:
Substances chimiques
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
CTLA-4 Antigen
0
CTLA4 protein, human
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4842-4851Subventions
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228414
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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