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

@article{Motzer2020AvelumabPA,
  title={Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial},
  author={R. Motzer and Paul B. Robbins and Thomas Powles and Laurence Albiges and John B.A.G. Haanen and James M. G. Larkin and Xinmeng Jasmine Mu and Keith A. Ching and Motohide Uemura and Sumanta Kumar Pal and Boris Y. Alekseev and Gwena{\"e}lle Gravis and Matthew T. Campbell and Konstantin Penkov and Jae Lyun Lee and Subramanian Hariharan and Xiao Wang and Weidong Zhang and Jing Wang and Aleksander Chudnovsky and Alessandra di Pietro and Amber C Donahue and Toni K. Choueiri},
  journal={Nature Medicine},
  year={2020},
  pages={1-9}
}
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… 

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Tumor molecular profiling 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.

Association of Neutrophil-to-Lymphocyte Ratio With Efficacy of First-Line Avelumab Plus Axitinib vs Sunitinib in Patients with Advanced Renal Cell Carcinoma Enrolled in the Phase 3 JAVELIN Renal 101 Trial.

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Current data support NLR as a prognostic biomarker in patients with advanced RCC receiving avelumab plus axit inib or sunitinib and tumor analyses showed an association between NLR and key biological characteristics, suggesting a role of NLR in underlying mechanisms influencing clinical outcome.

Biomarker analysis from CheckMate 214: nivolumab plus ipilimumab versus sunitinib in renal cell carcinoma

The exploratory analyses reveal relationships between molecular biomarkers and provide supportive data on how the inflammation status of the tumor microenvironment may be important for identifying predictive biomarkers of response and survival with combination immunotherapy in patients with RCC.

Association of AXL and PD-L1 Expression with Clinical Outcomes in Patients with Advanced Renal Cell Carcinoma Treated with PD-1 Blockade

The results show that high AXL-expression level in tumor cells is associated with lower response rates and a trend to shorter progression-free survival following anti-PD-1 treatment, and provide compelling support for screening both AXL and PD-L1 expression in the management of advanced ccRCC.

Molecular analysis and favorable clinical outcomes in real-world patients with metastatic renal cell carcinoma

Biomarker association with best overall response (BOR), progression-free survival (PFS), and overall survival (OS) were evaluated using multivariable modeling and data pointed at PD-L1 IHC and angiogenesis expression in ccRCC and hypoxia, glycolysis, and Angiogenesisexpression in nccRCC as potential prognostic factors.

Biomarkers 101 — personalizing therapy for RCC

A biomarker analysis of JAVELIN Renal 101 found that neither expression of the commonly assessed biomarker PDL1 nor tumour mutational burden differentiated PFS in either study arm, but the researchers also discovered a distinct signature of 26 mostly angiogenic genes involved in T cell and natural killer cell function, chemotaxis and/or inflammation.

CD44 Is Involved in Sunitinib Resistance and Poor Progression-free Survival After Sunitinib Treatment of Renal Cell Carcinoma

CD44 is involved in sunitinib resistance and may be a promising marker for sunit inib treatment in mRCC and this study validated the findings by in silico analysis.

Biomarkers 101 — personalizing therapy for RCC

A biomarker analysis of JAVELIN Renal 101 found that neither expression of the commonly assessed biomarker PDL1 nor tumour mutational burden differentiated PFS in either study arm, but the researchers also discovered a distinct signature of 26 mostly angiogenic genes that could predict outcomes in the sunitinib arm.
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