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

Toni K. Choueiri, David J. Figueroa, André P. Fay, Sabina Signoretti, Yuan Liu, Robert Gagnon, Keith Deen, Christopher Carpenter, Peter Benson, Thai H. Ho, Lini Pandite, Paul De Souza, Thomas Powles, Robert J. Motzer

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1071-1077
Number of pages7
JournalClinical Cancer Research
Volume21
Issue number5
DOIs
StatePublished - Mar 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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