irRECIST for the Evaluation of Candidate Biomarkers of Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma: Analysis of a Phase II Prospective Clinical Trial.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological
/ administration & dosage
Biomarkers, Tumor
CD8-Positive T-Lymphocytes
/ immunology
Carcinoma, Renal Cell
/ diagnosis
Female
Gene Expression
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Kidney Neoplasms
/ diagnosis
Lymphocytes, Tumor-Infiltrating
/ immunology
Male
Middle Aged
Nivolumab
/ administration & dosage
Odds Ratio
Prognosis
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:
01 04 2019
01 04 2019
Historique:
received:
02
10
2018
revised:
18
12
2018
accepted:
16
01
2019
pubmed:
24
1
2019
medline:
12
5
2020
entrez:
24
1
2019
Statut:
ppublish
Résumé
Immune-related RECIST (irRECIST) were designed to capture atypical responses seen with immunotherapy. We hypothesized that, in patients with metastatic clear cell renal cell carcinoma (mccRCC), candidate biomarkers for nivolumab response would show improved association with clinical endpoints capturing atypical responders (irRECIST) compared with standard clinical endpoints (RECISTv1.1). Endpoints based on RECISTv1.1 [objective response rate (ORR)/progression-free survival (PFS)] or irRECIST [immune-related ORR (irORR)/immune-related PFS (irPFS)] were compared in patients enrolled in the CheckMate-010 trial. Pretreatment tumors were analyzed by PD-L1 and PD-L2 IHC, and by multiplex immunofluorescence for CD8, PD-1, TIM-3, and LAG-3. T-cell activation signatures were assessed by RNA sequencing. Median irPFS was significantly longer than median PFS. irORR was not significantly different from ORR, but immune-related progressive disease (irPD) rate was significantly lower than progressive disease (PD) rate. Tumor cell (TC) PD-L1 expression was not associated with PFS or ORR, but patients with TC PD-L1 ≥1% had longer median irPFS and higher irORR. High percentage of CD8 Atypical responders to nivolumab were identified in the CheckMate-010 trial. We observed improved association of candidate biomarkers for nivolumab response with endpoints defined by irRECIST compared with RECISTv1.1. TC PD-L1 expression in combination with PD-1 expression on CD8
Identifiants
pubmed: 30670497
pii: 1078-0432.CCR-18-3206
doi: 10.1158/1078-0432.CCR-18-3206
pmc: PMC6445699
mid: NIHMS1519472
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Biomarkers, Tumor
0
Nivolumab
31YO63LBSN
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2174-2184Subventions
Organisme : NCI NIH HHS
ID : P50 CA101942
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009172
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA155010
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211482
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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