Tissue based biomarkers in non-clear cell RCC: Correlative analysis from the ASPEN clinical trial
Foo, W. C.
Stadler, W. M.
Jones, R. J.
Garcia, J. A.
Vaishampayan, U. N.
Hawkins, Robert E
Hainsworth, J. D.
Kollmannsberger, C. K.
Logan, T. F.
Pickering, L. M.
Ryan, C. W.
George, D. J.
Armstrong, A. J.
AffiliationDepartment of Biostatistics and Bioinformatics, Duke University, Durham NC
MetadataShow full item record
AbstractBiomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC treated with the mTOR inhibitor everolimus (n=57) or the vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib (n=51), stratified by MSKCC risk and histology. The primary endpoint was overall survival (OS) and secondary efficacy endpoints for this exploratory biomarker analysis were radiographic progression-free survival (rPFS) defined by intention-to-treat using the RECIST 1.1 criteria and radiographic response rates. Tissue biomarkers (n=78) of mTOR pathway activation (phospho-S6 and -Akt, c-kit) and VEGF pathway activation (HIF-1α, c-MET) were prospectively explored in tumor tissue by immunohistochemistry prior to treatment and associated with clinical outcomes. We found that S6 activation was more common in poor risk NC-RCC tumors and S6/Akt activation was associated with worse PFS and OS outcomes with both everolimus and sunitinib, while c-kit was commonly expressed in chromophobe tumors and associated with improved outcomes with both agents. C-MET was commonly expressed in papillary tumors and was associated with lower rates of radiographic response but did not predict PFS for either agent. In multivariable analysis, both pAkt and c-kit were statistically significant prognostic biomarkers of OS. No predictive biomarkers of treatment response were identified for clinical outcomes. Most biomarker subgroups had improved outcomes with sunitinib as compared to everolimus.
CitationHalabi S, Yang Q, Carmack A, Zhang S, Foo W-C, et al. Tissue based biomarkers in non-clear cell RCC: Correlative analysis from the ASPEN clinical trial [Internet]. Vol. 19, Kidney Cancer Journal. Kidney Cancer Association (KCA); 2021.
JournalKidney Cancer Journal
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