Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial.
Adolescent
Adult
Aged
Antibodies, Monoclonal
/ administration & dosage
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Axitinib
/ administration & dosage
Biomarkers, Tumor
/ genetics
Carcinoma, Renal Cell
/ drug therapy
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Kidney
/ drug effects
Male
Middle Aged
Progression-Free Survival
Sunitinib
/ administration & dosage
Transcriptome
Young Adult
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
29
01
2020
accepted:
03
08
2020
pubmed:
9
9
2020
medline:
9
1
2021
entrez:
8
9
2020
Statut:
ppublish
Résumé
We report on molecular analyses of baseline tumor samples from the phase 3 JAVELIN Renal 101 trial (n = 886; NCT02684006 ), which demonstrated significantly prolonged progression-free survival (PFS) with first-line avelumab + axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We found that neither expression of the commonly assessed biomarker programmed cell death ligand 1 (PD-L1) nor tumor mutational burden differentiated PFS in either study arm. Similarly, the presence of FcɣR single nucleotide polymorphisms was unimpactful. We identified important biological features associated with differential PFS between the treatment arms, including new immunomodulatory and angiogenesis gene expression signatures (GESs), previously undescribed mutational profiles and their corresponding GESs, and several HLA types. These findings provide insight into the determinants of response to combined PD-1/PD-L1 and angiogenic pathway inhibition and may aid in the development of strategies for improved patient care in aRCC.
Identifiants
pubmed: 32895571
doi: 10.1038/s41591-020-1044-8
pii: 10.1038/s41591-020-1044-8
pmc: PMC8493486
mid: NIHMS1737783
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Monoclonal, Humanized
0
Biomarkers, Tumor
0
Axitinib
C9LVQ0YUXG
avelumab
KXG2PJ551I
Sunitinib
V99T50803M
Banques de données
ClinicalTrials.gov
['NCT02684006']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1733-1741Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
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