KIM-1 was evaluated as plasma circulating biomarker of microscopical residual disease, disease recurrence after nephrectomy, and potential benefit from adjuvant immunotherapy (IO). No data are available about its role in the metastatic setting. Tide-A phase 2 trial showed the feasibility of a de-intensified strategy of VEGFR-TKI interruption and IO-maintenance in mRCC pts treated with ave+axi. We investigated whether plasma KIM-1 was a prognostic biomarker in the prospective cohort of Tide-A.
Materials & Methods
We performed a proteomics analysis with the aptamer-based technology SomaScan 7K (Somalogic, USA) to characterize the plasma expression levels of ≈7000 proteins. Levels of KIM-1 SomaScan aptamers (uniprot accession number Q96D42, aptamer ID:9021-1) were evaluated in available baseline samples and normalized by Adaptive Normalization by Maximum Likelihood (ANML) to integrate samples and correct for batch-effects. KIM-1 cut-off (10.456 relative fluorescence units [RFU]) was determined by Maximally Selected Rank Statistics using the maxstat R pack, with Van der Waerden test and log-rank scores methods. Outcomes in pts with high vs. low KIM-1 levels at baseline were analyzed in the overall population, and adjusted for IMDC groups and for the duration of ave-maintenance.
Results
Of 79 pts enrolled in Tide-A, data for KIM-1 analysis at baseline were available for 69 pts, of which 9 (13%) were KIM-1-high and 60 (87%) KM-1-low. KIM-1-high status was significantly associated with shorter OS (mOS 24.2 months [95%CI 21.1–NR] in KIM-1-high vs. NR in KIM-1-low; p=0.0019). The 2-yOS rate was 90% in KIM-1-low vs. 56% in KIM-1-high (p=0.002). Significant correlation between KIM-1 levels and OS was retained when adjusted for IMDC (table). No significant correlation was observed between KIM-1 levels and PFS (mPFS 22.9 vs. 29.9 months in KIM-1-high and low, respectively; p= 0.4). Of the 29 pts that discontinued axi, KIM-1 data were available for 28 pts; the median duration of ave-maintenance was 15.9 wks in 25 pts with KIM-1-low and NR in 3 pts with KIM-1-high (p=0.19).
2 – year OS (%)
KIM-1 High
KIM-1 Low
p value
IMDC Good
80
95
0.045
IMDC Int/Poor
25
86
0.006
High baseline plasma KIM-1 level is an independent negative prognostic factor in mRCC pts treated with VEGFR-TKI+IO, regardless from IMDC. KIM-1 seems not to have a key role in the selection of pts more likely to benefit from a TKI-intermittent strategy. Additional analyses are ongoing to identify predictive biomarkers for a tailored pts management.