Correlation of PDL1 tumor expression and outcomes in renal cell carcinoma (RCC) patients (pts) treated with pazopanib (paz).

Abstract

3021 Background: The interaction between PDL1 (B7H1) and its receptor PD-1 on activated T cells plays an important role in the inhibition of T-cell responses and contributes to suppression of antitumor immune responses. Tumor PDL1 expression has been associated with poor outcomes in RCC. This study investigates the correlation between PDL1 tumor expression and outcomes in RCC pts treated with paz. Methods: Using IHC, we retrospectively analyzed baseline FFPE tumor samples for PDL1 from 2 paz RCC studies: a single arm phase II trial and randomized placebo (pbo)-controlled phase III study. PDL1 expression was analyzed by MedTox Laboratories using the anti-PDL1 MouseIgG1 clone 5H1 (Thompson) on the Leica automated IHC platform. Additional dual PDL1/CD68 staining was carried out to delineate tumor and macrophage PDL1 expression. Tumor PDL1 expression was quantified by H-Score (HS) and PDL1+ macrophages were assessed semi-quantitatively. Association between PDL1H scores and PFS was investigated by Kaplan-Meier analysis using optimal cutoff of PDL1tumor HS (minimum p value, log rank test). Results: The optimal cut-point of PD-L1 tumor HS, relative to PFS, was identified as HS > 3. In the phase II study (46 available samples out of 225), HS range was 0-150 and most samples had negative (HS = 0, n = 34, 74%) or low (HS 1-3, n=4, 9%) PDL1 expression. Pts with HS > 3 (n = 8, 17%) had significantly shorter PFS (2.6 mo) than those with HS ≤ 3 (12 mo; p = .0005). In the phase III study (N = 160 available samples: paz, 113 of 290; pbo, 47 of 145), HS range was 0-280. Most patients had negative (n = 122/160, 76%) or low (n = 9/160, 6%) PD-L1 expression, with 18% (29/160) having HS > 3. Pbo-arm pts with HS > 3 (n = 6/47, 13%) had shorter PFS (2.3 vs 5.5 mo p = .0207). Paz-arm pts with HS > 3 (n = 23/113, 20%) trended toward shorter PFS (7.3 vs 11 mo, p = .1405). Conclusions: PDL1 appears to be a prognostic marker with PDL1 HS > 3 associated with shorter PFS. Limitations of the study include the retrospective nature of the analysis with limited pt samples available, low or negative PDL1 expression in the vast majority of pts, and use of archival samples that may not accurately reflect PDL1 status at study entry. Additional results (tumor volume, OS) will be presented.