Angiokines associated with targeted therapy outcomes in patients with non-clear cell renal cell carcinoma
AuthorsArmstrong, A. J.
Nixon, A. B.
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
AffiliationDuke University Department of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina.
MetadataShow full item record
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.
CitationArmstrong 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.
JournalClinical Cancer Research
- Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial.
- Authors: Armstrong AJ, Halabi S, Eisen T, Broderick S, 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, Lusk CM, Oberg S, George DJ
- Issue date: 2016 Mar
- Everolimus Versus Sunitinib Prospective Evaluation in Metastatic Non-Clear Cell Renal Cell Carcinoma (ESPN): A Randomized Multicenter Phase 2 Trial.
- Authors: Tannir NM, Jonasch E, Albiges L, Altinmakas E, Ng CS, Matin SF, Wang X, Qiao W, Dubauskas Lim Z, Tamboli P, Rao P, Sircar K, Karam JA, McDermott DF, Wood CG, Choueiri TK
- Issue date: 2016 May
- A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma.
- Authors: Fernández-Pello S, Hofmann F, Tahbaz R, Marconi L, Lam TB, Albiges L, Bensalah K, Canfield SE, Dabestani S, Giles RH, Hora M, Kuczyk MA, Merseburger AS, Powles T, Staehler M, Volpe A, Ljungberg B, Bex A
- Issue date: 2017 Mar
- Phase II trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4).
- Authors: Motzer RJ, Alyasova A, Ye D, Karpenko A, Li H, Alekseev B, Xie L, Kurteva G, Kowalyszyn R, Karyakin O, Neron Y, Cosgriff T, Collins L, Brechenmacher T, Lin C, Morgan L, Yang L
- Issue date: 2016 Mar
- Tissue based biomarkers in non-clear cell RCC: Correlative analysis from the ASPEN clinical trial.
- Authors: Halabi S, Yang Q, Carmack A, Zhang S, Foo WC, 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, Armstrong AJ
- Issue date: 2021 Oct