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

dc.contributor.authorArmstrong, Andrew J.
dc.contributor.authorNixon, Andrew B.
dc.contributor.authorCarmack, Andrea
dc.contributor.authorYang, Qian
dc.contributor.authorEisen, Tim
dc.contributor.authorStadler, Walter M.
dc.contributor.authorJones, Robert J.
dc.contributor.authorGarcia, Jorge A.
dc.contributor.authorVaishampayan, Ulka N.
dc.contributor.authorPicus, Joel
dc.contributor.authorHawkins, Robert E.
dc.contributor.authorHainsworth, John D.
dc.contributor.authorKollmannsberger, Christian K.
dc.contributor.authorLogan, Theodore F.
dc.contributor.authorPuzanov, Igor
dc.contributor.authorPickering, Lisa M.
dc.contributor.authorRyan, Christopher W.
dc.contributor.authorProtheroe, Andrew
dc.contributor.authorGeorge, Daniel J.
dc.contributor.authorHalabi, Susan
dc.contributor.departmentMedicine, School of Medicineen_US
dc.date.accessioned2022-11-22T17:49:54Z
dc.date.available2022-11-22T17:49:54Z
dc.date.issued2021-06
dc.description.abstractPURPOSE: 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.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationArmstrong, 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, R. 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. (2021). Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma. Clinical Cancer Research, 27(12), 3317–3328. https://doi.org/10.1158/1078-0432.CCR-20-4504en_US
dc.identifier.issn1078-0432, 1557-3265en_US
dc.identifier.urihttps://hdl.handle.net/1805/30607
dc.language.isoen_USen_US
dc.publisherAACRen_US
dc.relation.isversionof10.1158/1078-0432.CCR-20-4504en_US
dc.relation.journalClinical Cancer Researchen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectCarcinoma, Renal Cellen_US
dc.subjectPlacenta Growth Factoren_US
dc.subjectAntineoplastic Agentsen_US
dc.titleAngiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinomaen_US
dc.typeArticleen_US
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