Kidney injury molecule‐1 (KIM-1) in localized and metastatic renal cell carcinoma (RCC): A meta-analysis and systematic review.

539 Background: Kidney Injury Molecule‐1 (KIM‐1) is a type 1 cell membrane glycoprotein, currently under investigation as a biomarker in Renal Cell Carcinoma (RCC). In the adjuvant setting, high KIM-1 levels have been associated to worse outcomes, both in patients enrolled in the ASSURE trial (adjuvant sunitinib vs placebo) and CheckMate914 trial (nivolumab-ipilimumab vs placebo). Interestingly, in the IMotion010 trial, elevated plasma KIM-1 levels were found to be prognostic and predictive in patients treated with adjuvant atezolizumab. Basal KIM-1 levels have also been evaluated in metastatic RCC (mRCC), with lower levels being associated to a better prognosis. This meta-analysis and systematic review aim to clarify the prognostic role of KIM-1, both in adjuvant and metastatic settings. Methods: We conducted a meta-analysis and systematic review, including prospective clinical trials reporting outcomes based on basal KIM-1 levels, comparing patients with high versus low KIM-1 levels. A systematic literature search was performed using the MEDLINE and EMBASE databases. In the meta-analysis were included reports with outcomes data Hazard Ratio (HR) for Overall Survival (OS), Progression Free Survival (PFS), Disease Free Survival (DFS) according to baseline KIM-1 levels. Both adjuvant and mRCC trials were considered. The cutoff for KIM-1 high and low and the method to assess KIM-1 levels in each study was mandatory to include the data in our analysis. We identified two key primary endpoints: in the adjuvant setting, DFS according to baseline KIM-1 levels and in mRCC, PFS and OS according to basal KIM-1 levels. Results: We included data form 2120 patients enrolled in 4 randomized clinical trials (RCT), two in the metastatic setting (CheckMate-214, Javelin Renal 101) and two representatives of the adjuvant setting (Immotion010, ASSURE). The cutoffs used to define high and low baseline KIM-1 levels differed across trials, partly reflecting the different setting of the included trials. In adjuvant setting, we analyzed 961 patients and observed a DFS advantage for KIM-1 low patients (HR 0.57;95% CI 0.48-0.67). In metastatic setting, 1159 patients were included, showing OS advantage for the KIM-1 low subgroups (HR 0.63; 95% CI 0.51-0.87) but no statistically significant differences for PFS, although a numerical advantage for KIM-1 low patients (HR 0.52;95% CI 0.25-1.09). Conclusions: Data from our meta-analysis confirm the prognostic role of basal KIM-1 levels in both localized and mRCC. The main limitations of our analysis are the relatively small number of included trials and the heterogeneity in methods used to define high versus low KIM-1 levels across studies.