Correlation of PDL1 tumor expression and treatment outcomes in patients with renal cell carcinoma (RCC) receiving tyrosine kinase inhibitors: COMPARZ study analysis.

Abstract

416 Background: The interaction of PDL1 (B7H1) with its receptor PD-1 on activated T cells contributes to suppression of antitumor immune responses. Tumor PDL1 expression has been associated with poor outcomes in RCC but has not been investigated as a biomarker of response in RCC patients receiving standard vascular endothelial growth factor (VEGF)-targeted therapy. Methods: Formalin-fixed paraffin-embedded tumor samples were collected at baseline from consenting patients enrolled in COMPARZ—a phase lll clinical trial comparing pazopanib and sunitinib as first-line interventions for metastatic RCC (Motzer et al, NEJM 2013). PDL1 expression was evaluated using the anti-PDL1 mouseIgG1 (clone 5H1; Thompson) on the Leica automated immunohistochemistry platform. Additional dual PDL1/CD68 staining was performed on tumor associated macrophages (TAMs). Tumor PDL1 expression was quantified by an H-score (HS). PDL1+ TAMs were assessed semiquantitatively. In addition, intra-tumor CD8+ T cells were quantified morphometrically. The association between PDL1 HS, CD8+T cell counts, and survival was investigated using Kaplan-Meier analysis. Results: HS data were available from 453 of 1110 patients. 64% of patients had negative (HS = 0) PDL1 expression (HS range 0-290), but PDL1 expression was associated with tumours containing higher numbers of infiltrating macrophages. Peripheral CD8+ T cells in the invasive margin surrounding the tumor were also observed. Patients with HS >50 (n = 61, 13%) had significantly shorter overall survival (OS) in both pazopanib (19.7 vs 31.6 mo) and sunitinib (15.3 vs 27.7 mo) arms. In both arms, patients with HS >50 with intratumoral CD8+T cell counts >300 had the shortest OS. Results were similar for progression-free survival and persisted on multivariate analysis. Conclusions: This is the largest report to show that tumors’PDL1 expression and CD8+ T cell counts are associated with treatment outcome in metastatic RCC patients. Increased PDL1, or increased PDL1 plus tumor CD8+ T cell counts, were associated with shorter OS. These findings may have major implications for future trial designs that involve PD-1 inhibitors.