Abstract
Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma in the S-TRAC trial (ClinicalTrials.gov number, NCT00375674). A prospectively-designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of PD-L1, CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan–Meier method. For biomarkers with predictive potential, Receiver Operating Characteristics curves were generated. Results: Baseline characteristics were similar in patients with (n=191) and without (n=419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8+ T-cell density ≥ versus < median (median [95% CI], not reached [6.83–not reached] vs. 3.47 years [1.73–not reached]; hazard ratio 0.40 [95% CI, 0.20–0.81]; P=0.009) treated with sunitinib (n=101), but not with placebo (n=90). The sensitivity and specificity for CD8+ T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1+ versus PD-L1– tumors (hazard ratio 1.75; P=0.103). Among all patients with PD-L1+ tumors, DFS was numerically longer with sunitinib versus placebo (hazard ratio 0.58; P=0.175). Conclusions: Greater CD8+ T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk non-metastatic renal cell carcinoma should also be further explored.