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

Publication ,  Journal Article
Armstrong, AJ; Nixon, AB; Carmack, A; Yang, Q; Eisen, T; Stadler, WM; Jones, RJ; Garcia, JA; Vaishampayan, UN; Picus, J; Hawkins, RE; Ryan, CW ...
Published in: Clin Cancer Res
June 15, 2021

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.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

June 15, 2021

Volume

27

Issue

12

Start / End Page

3317 / 3328

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Pyrroles
  • Placenta Growth Factor
  • Oncology & Carcinogenesis
  • Lymphokines
  • Kidney Neoplasms
  • Humans
  • Female
  • Disease-Free Survival
  • Carcinoma, Renal Cell
 

Citation

APA
Chicago
ICMJE
MLA
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Armstrong, A. J., Nixon, A. B., Carmack, A., Yang, Q., Eisen, T., Stadler, W. M., … Halabi, S. (2021). Angiokines Associated with Targeted Therapy Outcomes in Patients with Non-Clear Cell Renal Cell Carcinoma. Clin Cancer Res, 27(12), 3317–3328. https://doi.org/10.1158/1078-0432.CCR-20-4504
Armstrong, Andrew J., Andrew B. Nixon, Andrea Carmack, Qian Yang, Tim Eisen, Walter M. Stadler, Robert J. Jones, et al. “Angiokines Associated with Targeted Therapy Outcomes in Patients with Non-Clear Cell Renal Cell Carcinoma.Clin Cancer Res 27, no. 12 (June 15, 2021): 3317–28. https://doi.org/10.1158/1078-0432.CCR-20-4504.
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 Jun 15;27(12):3317–28.
Armstrong, Andrew J., et al. “Angiokines Associated with Targeted Therapy Outcomes in Patients with Non-Clear Cell Renal Cell Carcinoma.Clin Cancer Res, vol. 27, no. 12, June 2021, pp. 3317–28. Pubmed, doi:10.1158/1078-0432.CCR-20-4504.
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. Angiokines Associated with Targeted Therapy Outcomes in Patients with Non-Clear Cell Renal Cell Carcinoma. Clin Cancer Res. 2021 Jun 15;27(12):3317–3328.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

June 15, 2021

Volume

27

Issue

12

Start / End Page

3317 / 3328

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Pyrroles
  • Placenta Growth Factor
  • Oncology & Carcinogenesis
  • Lymphokines
  • Kidney Neoplasms
  • Humans
  • Female
  • Disease-Free Survival
  • Carcinoma, Renal Cell