Soluble PD-L1 As a Marker of Progressive Disease on Nivolumab in Kidney Cancer
Journal of clinical oncology(2020)
摘要
746 Background: Higher levels of soluble PD-L1 (sPD-L1) are associated with poor prognosis in patients with solid tumors including in renal cell carcinoma (RCC). Here we have tested whether in patients with advanced RCC, sPD-L1 levels are associated with PD-L1 expression on tumor tissue or with clinical outcomes on PD-1 blockade. Methods: Serum from 91 patients with advanced clear-cell RCC on a biomarker study of nivolumab (NCT01358721) obtained at baseline (Day 1), Day 29 and Day 63, was tested by SiMoa™ for sPD-L1 (capture mAb 298.12B1, detection mAb 339.4C10; Freeman laboratory and Quanterix). Tumor PD-L1 (tPD-L1) was assessed on pretreatment biopsies (Dako). Association of sPDL1 and tPD-L1 with clinical outcomes was analyzed, including best overall response by RECIST (BOR), objective response of >20% (OR), progression free survival (PFS), and overall survival (OS). Results quote Wilcoxon Rank Sum test or paired t-test with significance at P < 0.05. Results: Median sPD-L1 was highest in patients with progressive disease (PD) at all timepoints (Table). Compared to baseline, sPD-L1 levels significantly increased in patients with PD on Day 29 and Day 63, while sPD-L1 levels significantly decreased in patients with CR/PR on Day 63. In addition, we found significantly higher baseline sPD-L1 in patients with prior therapy compared to those who were treatment-naïve. High tPD-L1 was weakly associated with favorable OR, but also weakly associated with high baseline sPD-L1. Conclusions: Unlike tPD-L1, sPD-L1 levels may show promise for association with clinical response to nivolumab in RCC. In this exploratory study, sPD-L1 increase on-treatment was significantly associated with lack of OR, and may be of utility as an early marker for PD worthy of future validation. Analysis of RNASeq from patients’ tumor specimen is underway to assess whether high sPD-L1 with PD is associated with immune suppressive signatures.[Table: see text]
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