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Plasma KIM-1 is associated with clinical outcomes after resection for localized renal cell carcinoma: A trial of the ECOG-ACRIN Research Group (E2805)

Date

30 Sep 2019

Session

Poster Display session 3

Presenters

Wenxin Xu

Citation

Annals of Oncology (2019) 30 (suppl_5): v25-v54. 10.1093/annonc/mdz239

Authors

W. Xu1, M. Puligandla2, N.B. Haas3, K.T. Flaherty4, R.G. Uzzo5, V. Sabbisetti6, J.J. Dutcher7, R.S. DiPaola8, R.S. Bhatt9

Author affiliations

  • 1 Medical Oncology, Beth Israel Deaconess Med. Center, 02215 - Boston/US
  • 2 Statistics, ECOG-ACRIN Biostatistics Center, 02215 - Boston/US
  • 3 Hematology Oncology, University of Pennsylvania/Abramson Cancer Center, 19104 - Philadelphia/US
  • 4 Hematology/oncology, Massachusetts General Hospital, Harvard Medical School, 02114 - Boston/US
  • 5 Urologic Oncology, Fox Chase Cancer Center, Philadelphia/US
  • 6 Pathology, Brigham and Women's Hospital, Boston/US
  • 7 Renal Sub-committee, Cancer Research Foundation, Chappaqua/US
  • 8 Medical Oncology, University of Kentucky, 40536 - Lexington/US
  • 9 Medical Oncology, Beth Israel Deaconess Med. Center, Boston/US
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Background

There is currently no circulating biomarker for renal cell carcinoma (RCC). The use of adjuvant sunitinib for RCC after nephrectomy is controversial, and a biomarker could help to select the patients at highest risk for recurrence. Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain can be detected in circulating plasma. We therefore investigated whether KIM-1 is associated with worse outcomes in patients with localized RCC after nephrectomy.

Methods

In the ECOG-ACRIN 2805 (ASSURE) trial, 1943 patients with resected high-risk RCC were randomized 1:1:1 to sunitinib, sorafenib, or placebo. Post-nephrectomy baseline samples from 182 randomly selected patients (9.4% of the study population) was available for this post-hoc biomarker analysis. Samples were analyzed using a previously validated microbead-based assay. Kaplan-Meier and Cox proportional hazards models were used to test for association between circulating KIM-1 and disease free survival (DFS) as well as overall survival (OS). ROC analysis was performed to evaluate test characteristics for KIM-1 in predicting RCC recurrence within 6 months after nephrectomy.

Results

Higher KIM-1 levels were associated with worse DFS and OS after nephrectomy. This association remained independently significant after controlling for pathologic stage, sarcomatoid features, and Fuhrman grade (DFS: HR 1.20 per log increase in KIM-1, 95% CI 1.09-1.33, p < 0.001; OS: HR 1.27 per log increase in KIM-1, 95% CI 1.11-1.45, p < 0.001). These associations were independent of treatment arm. In Kaplan-Meier analysis using KIM-1 quartiles, higher quartiles of KIM-1 were associated with worse DFS and OS (log-rank p = 0.02 for both). Post-nephrectomy KIM-1 was a prognostic marker for disease recurrence within 6 months after nephrectomy (AUC 0.85).

Conclusions

Elevated plasma KIM-1 is associated with worse DFS and OS in patients with resected RCC, and therefore has potential as an adjuvant biomarker. Analysis of larger cohorts to confirm this association is underway.

Clinical trial identification

NCT00326898.

Editorial acknowledgement

Legal entity responsible for the study

ECOG-ACRIN Cancer Research Group (Peter J. O’Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs).

Funding

National Cancer Institute of the National Institutes of Health under the following award numbers: CA180820, CA180794, CA180867, CA189859.

Disclosure

K.T. Flaherty: Officer / Board of Directors: Loxo Oncology; Officer / Board of Directors: Clovis Oncology; Officer / Board of Directors: Strata Oncology; Officer / Board of Directors: Vivid Biosciences; Advisory / Consultancy, Corporate Advisory Board: X4 Pharmaceuticals; Advisory / Consultancy, Corporate Advisory Board: PIC Therapeutics; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Asana; Advisory / Consultancy: Adaptimmune; Advisory / Consultancy: Fount; Advisory / Consultancy: Aeglea; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Shattuck Labs; Advisory / Consultancy: Arch Oncology; Advisory / Consultancy: Tolero; Advisory / Consultancy: Apricity; Advisory / Consultancy: Oncoceutics; Advisory / Consultancy: Fog Pharma; Advisory / Consultancy, Checkmate, Boston Biomedical, Pierre Fabre, Cell Medica, and Debiopharm.: Others; Advisory / Consultancy: Neon Therapeutics; Advisory / Consultancy: Tvardi; Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck; Advisory / Consultancy: Takeda; Advisory / Consultancy: Verastem. V. Sabbisetti: Non-remunerated activity/ies, Patents on blood KIM-1 is a diagnostic, prognostic and predictive biomarker of RCC: Other. All other authors have declared no conflicts of interest.

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