In this paper, we evaluated KIM-1 as a biomarker in the IMmotion010 trial, which was a phase 3 randomized trial comparing adjuvant atezolizumab versus placebo. Among a panel of nearly 3,000 circulating proteins, we found that KIM-1 was the most strongly associated with recurrence after surgery. Patients who had high KIM-1 had better DFS on atezolizumab versus placebo, but this was not seen among patients with low KIM-1. This is potentially important because it shows that KIM-1 could be a useful blood biomarker for selecting patients for adjuvant immunotherapy.
We also found that longitudinal changes in KIM-1 were associated with outcomes. Patients who had an increase in KIM-1 during follow-up were more likely to have RCC recurrence. Baseline transcriptomic analyses showed that among high KIM-1 patients, expression of genes related to T cell function was associated with better DFS outcomes on atezolizumab.
Overall, our data shows for the first time that a blood-based biomarker can identify patients who benefit from adjuvant immunotherapy in RCC. This suggests that post-nephrectomy KIM-1 is both prognostic and predictive, and supports prospective validation of this biomarker as a decision-making tool for adjuvant therapy in future trials.
Written by: Wenxin Xu, MD, Oncologist, Dana-Farber Cancer Institute, Boston, MA
References:
- Xu W, Puligandla M, Halbert B, Haas NB, Flaherty KT, Uzzo RG, et al. Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma: A trial of the ECOG-ACRIN Research Group (E2805). Clin Cancer Res. April 8, 2021;
- Vemula SV, Xu W, Wang Y, Liu X, De Somocurcio JR, McDermott D, et al. Abstract 5151: High serum kidney injury marker-1 and high baseline tumor PD-L1 protein expression levels are independently associated with treatment effect in adjuvant nivolumab plus ipilimumab vs placebo in localized clear cell renal cell carcinoma. Cancer Research. March 22, 2024;84(6_Supplement):5151–5151.
- Xu W, Vemula SV, Motzer RJ, Chhibber A, Chowbene D, Perrot N, et al. Evaluation of circulating kidney injury marker-1 (KIM-1) as a prognostic and predictive biomarker in advanced renal cell carcinoma (aRCC): Post-hoc analysis of CheckMate 214. JCO. February 10, 2025;43(5_suppl):437–437.
- Xu W, Gaborieau V, Niman SM, Mukeria A, Liu X, Maremanda KP, et al. Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With Clinical Outcomes. JCO. May 3, 2024;JCO.23.00699.
- Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, et al. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. April 18, 2024;390(15):1359–1371.