Angiogenic factor and cytokine analysis among patients treated with adjuvant VEGFR TKIs in resected renal cell carcinoma

Wenxin Xu, Maneka Puligandla, Judith Manola, Andrea J. Bullock, Daniel Tamasauskas, David F. McDermott, Michael B. Atkins, Naomi B. Haas, Keith Flaherty, Robert G. Uzzo, Janice P. Dutcher, Robert S. DiPaola, Rupal S. Bhatt

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Purpose: The use of VEGFR TKIs for the adjuvant treatment of renal cell carcinoma (RCC) remains controversial. We investigated the effects of adjuvant VEGFR TKIs on circulating cytokines in the ECOG-ACRIN 2805 (ASSURE) trial. Experimental Design: Patients with resected high-risk RCC were randomized to sunitinib, sorafenib, or placebo. Plasma from 413 patients was analyzed from post-nephrectomy baseline, 4 weeks, and 6 weeks after treatment initiation. Mixed effects and Cox proportional hazards models were used to test for changes in circulating cytokines and associations between disease-free survival (DFS) and cytokine levels. Results: VEGF and PlGF increased after 4 weeks on sunitinib or sorafenib (P < 0.0001 for both) and returned to baseline at 6 weeks on sunitinib (corresponding to the break in the sunitinib schedule) but not sorafenib (which was administered continuously). sFLT-1 decreased after 4 weeks on sunitinib and 6 weeks on sorafenib (P < 0.0001). sVEGFR-2 decreased after both 4 and 6 weeks of treatment on sunitinib or sorafenib (P < 0.0001). Patients receiving placebo had no significant changes in cytokine levels. CXCL10 was elevated at 4 and 6 weeks on sunitinib and sorafenib but not on placebo. Higher baseline CXCL10 was associated with worse DFS (HR 1.41 per log increase in CXCL10, Bonferroni-adjusted P ¼ 0.003). This remained significant after adjustment for T-stage, Fuhrman grade, and ECOG performance status. Conclusions: Among patients treated with adjuvant VEGFR TKIs for RCC, drug-host interactions mediate changes in circulating cytokines. Elevated baseline CXCL10 was associated with worse DFS. Studies to understand functional consequences of these changes are under way.

Original languageEnglish
Pages (from-to)6098-6106
Number of pages9
JournalClinical Cancer Research
Volume25
Issue number20
DOIs
StatePublished - Oct 15 2019

Bibliographical note

Publisher Copyright:
© 2019 American Association for Cancer Research.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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