TY - JOUR
T1 - Correlation of PD-L1 tumor expression and treatment outcomes in patients with renal cell carcinoma receiving sunitinib or pazopanib
T2 - Results from COMPARZ, a randomized controlled trial
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.
N1 - Publisher Copyright:
© 2014 AACR.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Purpose: The interaction of programmed death-1 ligand (PDL1) 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 Hscore (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.
AB - Purpose: The interaction of programmed death-1 ligand (PDL1) 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 Hscore (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.
UR - http://www.scopus.com/inward/record.url?scp=84925969185&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925969185&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-14-1993
DO - 10.1158/1078-0432.CCR-14-1993
M3 - Article
C2 - 25538263
AN - SCOPUS:84925969185
SN - 1078-0432
VL - 21
SP - 1071
EP - 1077
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -