| Literature DB >> 32895571 |
Robert J Motzer1, Paul B Robbins2, Thomas Powles3, Laurence Albiges4, John B Haanen5, James Larkin6, Xinmeng Jasmine Mu7, Keith A Ching7, Motohide Uemura8, Sumanta K Pal9, Boris Alekseev10, Gwenaelle Gravis11, Matthew T Campbell12, Konstantin Penkov13, Jae Lyun Lee14, Subramanian Hariharan15, Xiao Wang7,16, Weidong Zhang17,18, Jing Wang17, Aleksander Chudnovsky19,20, Alessandra di Pietro21, Amber C Donahue22, Toni K Choueiri23.
Abstract
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.Entities:
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Year: 2020 PMID： 32895571 PMCID： PMC8493486 DOI： 10.1038/s41591-020-1044-8
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440