Concordance between PD-L1 assays for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC).

Abstract

577 Background: Immune checkpoint inhibitors (ICIs) are now standard of care for mRCC and mUC patients (pts). PD-L1 status is gaining importance as a predictive biomarker, particularly for cisplatin-ineligible mUC. Four different PD-L1 assays vary in thresholds of PD-L1 positivity dependent on tumor type, with limited concordance studies. Given real-world limitations in PD-L1 testing, concordance between assays are needed to distinguish positive (pos)/negative (neg) results and treatment selection. We undertook comparisons of Dako 28–8 and Ventana SP142 assays in mRCC and Dako 22C3 and Ventana SP263 assays in mUC. Methods: 32 patients with mRCC and 18 patients with mUC who had received ICI therapy at Duke Cancer Institute were identified. FFPE archival tumor samples for pts with mRCC were evaluated with Dako 28–8 and Ventana SP142 PD-L1 immunohistochemistry (IHC) assays. For pts with mUC, FFPE archival tumor samples were evaluated with Dako 22C3 and Ventana SP263 PD-L1 IHC assays. Scoring was validated by two pathologists using the scoring system for each assay. PD-L1 status was subsequently correlated to best RECIST response (objective response rate (ORR) defined as stable disease or better)). Results: The majority of mRCC cases (29/32, 91%) were concordant between Dako 28-8 and Ventana SP142 assays (8 cases pos and 21 cases neg), with 3 discordant cases (1 case pos for Dako 28-8 but neg for Ventana SP142 and 2 cases neg for Dako 28-8 but pos for Ventana SP142). The majority of mUC cases (17/18, 94%) were also concordant between Dako 22C3 and Ventana SP263 assays (2 pos cases and 15 neg cases), with 1 indeterminate Dako 22C3 test due to background lymph node. In mRCC, the ORR for PD-L1 pos cases was 45% (5/11) versus 33% (8/24) for PD-L1 neg cases. In mUC, the ORR for PD-L1 positive cases was 50% (1/2) versus 31% (5/16) for PD-L1 neg cases. Conclusions: There was strong concordance between PD-L1 tumor/immune cell assays chosen for comparison in both mRCC and mUC with similar performance characteristics. Although PD-L1 positivity enriches for response to ICIs, many patients respond who are PD-L1 negative. PD-L1 status could be used interchangeably for the majority of cases when selecting treatment in mRCC and mUC.