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

Abstract

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 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 ¼ 0). Patients with HS > 55 (n ¼ 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 ¼ 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.

The Association Between PD-L1 Expression and the Clinical Outcomes to Vascular Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Clear Cell Renal Cell Carcinoma

“…The Oncologist ® also showed that increased tumor PD-L1 expression was associated with shorter survival in mRCC patients receiving VEGF-TKI treatment [18,19]. However, unlike previous studies, the present study analyzed the predictive and prognostic implication of PD-Ls for VEGF-TKI therapy in comparison with various clinicopathological features associated with aggressive tumor behavior including pT stage, grade, tumor necrosis, vascular invasion, and sarcomatoid features.…”

Higher preoperative serum levels of PD‐L1 and B7‐H4 are associated with invasive and metastatic potential and predictable for poor response to VEGF‐targeted therapy and unfavorable prognosis of renal cell carcinoma

“…However, it remains challenging to select patients who are likely to respond to anti‐PD‐1/PD‐L1 therapy 12. In the COMPARZ trial, RCC patients received sunitinib or pazopanib therapy and increased immunohistochemical tumor cell PD‐L1 expression was associated with shorter survival 25. In this study, higher preoperative serum level of PD‐L1 was correlated with poorer differentiation, invasive and metastasis profiles, and shorter overall survival, and was independent prognostic factors for overall survival.…”

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

“…Both PD-L1 and CD8 expression are of prognostic significance in renal cancer 17 . These results underline the potential immunogenic effects of VEGF TKIs and the problems associated with archived untreated tissue for PD-L1 biomarker analysis in VEGF resistant ccRCC 14 .…”