Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial

被引：348

作者：

Motzer, Robert J. ^{[1
]}

Robbins, Paul B. ^{[2
]}

Powles, Thomas ^{[3
]}

Albiges, Laurence ^{[4
]}

Haanen, John B. ^{[5
]}

Larkin, James ^{[6
]}

Mu, Xinmeng Jasmine ^{[7
]}

Ching, Keith A. ^{[7
]}

Uemura, Motohide ^{[8
]}

Pal, Sumanta K. ^{[9
]}

Alekseev, Boris ^{[10
]}

Gravis, Gwenaelle ^{[11
]}

Campbell, Matthew T. ^{[12
]}

Penkov, Konstantin ^{[13
]}

Lee, Jae Lyun ^{[14
]}

Hariharan, Subramanian ^{[15
]}

Wang, Xiao ^{[7
,22
]}

Zhang, Weidong ^{[16
,23
]}

Wang, Jing ^{[16
]}

Chudnovsky, Aleksander ^{[17
,24
]}

di Pietro, Alessandra ^{[18
]}

Donahue, Amber C. ^{[19
]}

Choueiri, Toni K. ^{[20
,21
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, 1275 York Ave, New York, NY 10021 USA

[2] Pfizer, Translat Oncol, San Diego, CA USA

[3] Queen Mary Univ London, St Bartholomews Hosp, Dept Genitourinary Oncol, Barts Canc Inst,Expt Canc Med Ctr, London, England

[4] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France

[5] Netherlands Canc Inst, Div Med Oncol, Amsterdam, Netherlands

[6] Royal Marsden NHS Fdn Trust, London, England

[7] Pfizer, Computat Biol, San Diego, CA USA

[8] Osaka Univ Hosp, Grad Sch Med, Osaka, Japan

[9] City Hope Comprehens Canc Ctr, Dept Med Oncol, Duarte, CA USA

[10] Moscow Sci Res Oncol Inst, Sci, Moscow, Russia

[11] Inst Paoli Calmettes, Dept Med Oncol, Marseille, France

[12] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

[13] Euromedserv, Private Med Inst, St Petersburg, Russia

[14] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea

[15] Pfizer, Oncol, New York, NY USA

[16] Pfizer, Biostat, Cambridge, MA USA

[17] Pfizer, Oncol, Cambridge, MA USA

[18] Pfizer, Immunooncol, Milan, Italy

[19] Pfizer, Translat Oncol, La Jolla, CA USA

[20] Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA

[21] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[22] Lyell Immunopharma, San Francisco, CA USA

[23] Jounce Therapeut, Cambridge, MA USA

[24] Ipsen, Cambridge, MA USA

来源：

NATURE MEDICINE | 2020年 / 26卷 / 11期

关键词：

TUMOR; CANCER; EXPRESSION; LANDSCAPE;

D O I：

10.1038/s41591-020-1044-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Fc gamma R 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.

引用

页码：1733 / +

页数：22

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