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    Angiokines associated with targeted therapy outcomes in patients with non-clear cell renal cell carcinoma

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    Authors
    Armstrong, A. J.
    Nixon, A. B.
    Carmack, A.
    Yang, Q.
    Eisen, T.
    Stadler, W. M.
    Jones, R. J.
    Garcia, J. A.
    Vaishampayan, U. N.
    Picus, J.
    Hawkins, Robert E
    Hainsworth, J. D.
    Kollmannsberger, C. K.
    Logan, T. F.
    Puzanov, I.
    Pickering, L. M.
    Ryan, C. W.
    Protheroe, A.
    George, D. J
    Halabi, S.
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    Affiliation
    Duke University Department of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina.
    Issue Date
    2021
    
    Metadata
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    Abstract
    Purpose: Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC) to inform treatment selection but also to identify novel therapeutic targets. We thus sought to profile circulating angiokines in the context of a randomized treatment trial of everolimus versus sunitinib. Patients and methods: ASPEN (NCT01108445) was an international, randomized, open-label phase II trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC with no prior systemic therapy. Patients were randomized to everolimus or sunitinib and treated until disease progression or unacceptable toxicity. The primary endpoint was radiographic progression-free survival (PFS) defined by RECIST 1.1. Plasma angiokines were collected at baseline, cycle 3, and progression and associated with PFS and overall survival (OS). Results: We enrolled 108 patients, 51 received sunitinib and 57 everolimus; of these, 99 patients had evaluable plasma for 23 angiokines. At the final data cutoff, 94 PFS and 64 mortality events had occurred. Angiokines that were independently adversely prognostic for OS were osteopontin (OPN), TIMP-1, thrombospondin-2 (TSP-2), hepatocyte growth factor (HGF), and VCAM-1, and these were also associated with poor-risk disease. Stromal derived factor 1 (SDF-1) was associated with improved survival. OPN was also significantly associated with worse PFS. No statistically significant angiokine-treatment outcome interactions were observed for sunitinib or everolimus. Angiopoeitin-2 (Ang-2), CD-73, HER-3, HGF, IL6, OPN, PIGF, PDGF-AA, PDGF-BB, SDF-1, TGF-b1-b2, TGFb-R3, TIMP-1, TSP-2, VCAM-1, VEGF, and VEGF-R1 levels increased with progression on everolimus, while CD-73, ICAM-1, IL6, OPN, PlGF, SDF-1, TGF-b2, TGFb-R3, TIMP-1, TSP-2, VEGF, VEGF-D, and VCAM-1 increased with progression on sunitinib. Conclusions: In patients with metastatic NC-RCC, we identified several poor prognosis angiokines and immunomodulatory chemokines during treatment with sunitinib or everolimus, particularly OPN.
    Citation
    Armstrong AJ, Nixon AB, Carmack A, Yang Q, Eisen T, Stadler WM, et al. Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma. Clin Cancer Res. 2021 Feb 16;27(12):3317–28.
    Journal
    Clinical Cancer Research
    URI
    http://hdl.handle.net/10541/624461
    DOI
    10.1158/1078-0432.Ccr-20-4504
    PubMed ID
    33593885
    Additional Links
    https://dx.doi.org/10.1158/1078-0432.Ccr-20-4504
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1158/1078-0432.Ccr-20-4504
    Scopus Count
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