PT  - JOURNAL ARTICLE
AU  - Choueiri, Toni K.
AU  - Figueroa, David J.
AU  - Fay, André P.
AU  - Signoretti, Sabina
AU  - Liu, Yuan
AU  - Gagnon, Robert
AU  - Deen, Keith
AU  - Carpenter, Christopher
AU  - Benson, Peter
AU  - Ho, Thai H.
AU  - Pandite, Lini
AU  - de Souza, Paul
AU  - Powles, Thomas
AU  - Motzer, Robert J.
TI  - Correlation of PD-L1 Tumor Expression and Treatment Outcomes in Patients with Renal Cell Carcinoma Receiving Sunitinib or Pazopanib: Results from COMPARZ, a Randomized Controlled Trial
AID  - 10.1158/1078-0432.CCR-14-1993
DP  - 2015 Mar 01
TA  - Clinical Cancer Research
PG  - 1071--1077
VI  - 21
IP  - 5
4099  - http://clincancerres.aacrjournals.org/content/21/5/1071.short
4100  - http://clincancerres.aacrjournals.org/content/21/5/1071.full
SO  - Clin Cancer Res2015 Mar 01; 21
AB  - Purpose: The interaction of programmed death-1 ligand (PD-L1) with its receptor (PD-1) on T cells inactivates antitumor immune responses. PD-L1 expression has been associated with poor outcomes in renal cell carcinoma (RCC) but has not been investigated in advanced RCC patients receiving VEGF-targeted therapy. Experimental Design: Formalin-fixed paraffin-embedded specimens were collected at baseline from patients in the COMPARZ trial. Tumor cell PD-L1 expression by IHC was evaluated using H-score (HS). Dual PD-L1/CD68 staining was used to differentiate PD-L1 tumor expression from tumor-associated macrophages. Intratumor CD8-positive T cells were quantified morphometrically. Associations between biomarkers and survival were investigated using the log-rank test. Results: HS data were available from 453 of 1,110 patients. Sixty-four percent of patients had negative PD-L1 expression (HS = 0). Patients with HS > 55 (n = 59, 13%) had significantly shorter overall survival (OS) than those with HS ≤ 55 in both pazopanib and sunitinib arms (median 15.1 vs. 35.6 and 15.3 vs. 27.8 months, respectively, P = 0.03). In both arms, median OS was shortest in patients with HS > 55 and intratumor CD8-positive T-cell counts > 300 (9.6 and 11.9 months with pazopanib and sunitinib, respectively). Median OS in patients with HS ≤ 55 and CD8-positive T-cell counts ≤ 300 was 36.8 and 28.0 months with pazopanib and sunitinib, respectively. Progression-free survival results were similar to OS results. Conclusions: Increased tumor cell PD-L1, or PD-L1 plus tumor CD8-positive T-cell counts, were associated with shorter survival in patients with metastatic RCC receiving VEGF-targeted agents. These findings may have implications for future design of randomized clinical trials in advanced RCC. Clin Cancer Res; 21(5); 1071–7. ©2014 AACR.