TY - JOUR
T1 - Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma
T2 - biomarker analysis of the phase 3 JAVELIN Renal 101 trial
AU - Motzer, Robert J.
AU - Robbins, Paul B.
AU - Powles, Thomas
AU - Albiges, Laurence
AU - Haanen, John B.
AU - Larkin, James
AU - Mu, Xinmeng Jasmine
AU - Ching, Keith A.
AU - Uemura, Motohide
AU - Pal, Sumanta K.
AU - Alekseev, Boris
AU - Gravis, Gwenaelle
AU - Campbell, Matthew T.
AU - Penkov, Konstantin
AU - Lee, Jae Lyun
AU - Hariharan, Subramanian
AU - Wang, Xiao
AU - Zhang, Weidong
AU - Wang, Jing
AU - Chudnovsky, Aleksander
AU - di Pietro, Alessandra
AU - Donahue, Amber C.
AU - Choueiri, Toni K.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85090312744&partnerID=8YFLogxK
U2 - 10.1038/s41591-020-1044-8
DO - 10.1038/s41591-020-1044-8
M3 - Article
C2 - 32895571
AN - SCOPUS:85090312744
SN - 1078-8956
VL - 26
SP - 1733
EP - 1741
JO - Nature Medicine
JF - Nature Medicine
IS - 11
ER -