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Data from Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma

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Armstrong, AJ; Nixon, AB; Carmack, A; Yang, Q; Eisen, T; Stadler, WM; Jones, RJ; Garcia, JA; Vaishampayan, UN; Picus, J; Hawkins, RE; Ryan, CW ...
March 31, 2023

<div>AbstractPurpose:<p>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.</p>Patients and Methods:<p>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).</p>Results:<p>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.</p>Conclusions:<p>In patients with metastatic NC-RCC, we identified several poor prognosis angiokines and immunomodulatory chemokines during treatment with sunitinib or everolimus, particularly OPN.</p></div>

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Publication Date

March 31, 2023
 

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Armstrong, A. J., Nixon, A. B., Carmack, A., Yang, Q., Eisen, T., Stadler, W. M., … Halabi, S. (2023). Data from Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma. https://doi.org/10.1158/1078-0432.c.6530027
Armstrong, Andrew J., Andrew B. Nixon, Andrea Carmack, Qian Yang, Tim Eisen, Walter M. Stadler, Robert J. Jones, et al. “Data from Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma,” March 31, 2023. https://doi.org/10.1158/1078-0432.c.6530027.
Armstrong AJ, Nixon AB, Carmack A, Yang Q, Eisen T, Stadler WM, et al. Data from Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma. 2023.
Armstrong, Andrew J., et al. Data from Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma. 31 Mar. 2023. Crossref, doi:10.1158/1078-0432.c.6530027.
Armstrong AJ, Nixon AB, Carmack A, Yang Q, Eisen T, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, George DJ, Halabi S. Data from Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma. 2023.

DOI

Publication Date

March 31, 2023