Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial

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• dc.contributor.author Powles, Thomas
• dc.contributor.author Sridhar, Srikala S.
• dc.contributor.author Loriot, Yohann
• dc.contributor.author Bellmunt Molins, Joaquim, 1959-
• dc.contributor.author Mu, Xinmeng Jasmine
• dc.contributor.author Ching, Keith A.
• dc.contributor.author Pu, Jie
• dc.contributor.author Sternberg, Cora N.
• dc.contributor.author Petrylak, Daniel P.
• dc.contributor.author Tambaro, Rosa
• dc.contributor.author Dourthe, Louis M.
• dc.contributor.author Alvarez-Fernandez, Carlos
• dc.contributor.author Aarts, Maureen
• dc.contributor.author Di Pietro, Alessandra
• dc.contributor.author Grivas, Petros
• dc.contributor.author Davis, Craig B.
• dc.date.accessioned 2022-09-15T07:13:42Z
• dc.date.available 2022-09-15T07:13:42Z
• dc.date.issued 2021
• dc.description.abstract In a recent phase 3 randomized trial of 700 patients with advanced urothelial cancer (JAVELIN Bladder 100; NCT02603432 ), avelumab/best supportive care (BSC) significantly prolonged overall survival relative to BSC alone as maintenance therapy after first-line chemotherapy. Exploratory biomarker analyses were performed to identify biological pathways that might affect survival benefit. Tumor molecular profiling by immunohistochemistry, whole-exome sequencing and whole-transcriptome sequencing revealed that avelumab survival benefit was positively associated with PD-L1 expression by tumor cells, tumor mutational burden, APOBEC mutation signatures, expression of genes underlying innate and adaptive immune activity and the number of alleles encoding high-affinity variants of activating Fcγ receptors. Pathways connected to tissue growth and angiogenesis might have been associated with reduced survival benefit. Individual biomarkers did not comprehensively identify patients who could benefit from therapy; however, multi-parameter models incorporating genomic alteration, immune responses and tumor growth showed promising predictive utility. These results characterize the complex biologic pathways underlying survival benefit from immune checkpoint inhibition in advanced urothelial cancer and suggest that multiple biomarkers might be needed to identify patients who would benefit from treatment.
• dc.format.mimetype application/pdf
• dc.identifier.citation Powles T, Sridhar SS, Loriot Y, Bellmunt J, Mu XJ, Ching KA, et al. Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial. Nat Med. 2021 Dec; 27(12): 2200-11. DOI: 10.1038/s41591-021-01579-0
• dc.identifier.doi http://dx.doi.org/10.1038/s41591-021-01579-0
• dc.identifier.issn 1078-8956
• dc.identifier.uri http://hdl.handle.net/10230/54073
• dc.language.iso eng
• dc.publisher Nature Research
• dc.rights © Springer Nature Publishing AG Powles T, Sridhar SS, Loriot Y, Bellmunt J, Mu XJ, Ching KA, et al. Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial. Nat Med. 2021 Dec; 27(12): 2200-11, http://dx.doi.org/10.1038/s41591-021-01579-0
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Marcadors bioquímics
• dc.subject.other Càncer
• dc.subject.other Bufeta--Càncer--Tractament
• dc.title Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion