Immune biomarkers predictive for disease-free survival with adjuvant sunitinib in high-risk locoregional renal cell carcinoma: from randomized phase III S-TRAC study.

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.

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.

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).

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.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2018 Jan 26 [Epub ahead of print]

Daniel J George, Jean-Francois Martini, Michael Staehler, Robert J Motzer, Ahmed Magheli, Bernard Escudier, Paola Gerletti, Sherry Li, Michelle Casy, Brigitte Laguerre, Hardev Pandha, Allan Pantuck, Anup Patel, Maria J Lechuga, Alain Ravaud

Departments of Medicine and Surgery, Duke University, Duke Cancer Institute ., Translational Oncology, Pfizer Inc., Hospital of Munich., Department of Medicine, Memorial Sloan Kettering Cancer Center., Charité Universitaetsmedizin Berlin., Institut Gustave Roussy., Clinical Development and Medical Affairs, Pfizer Oncology., Oncology Statistics, Pfizer., Pfizer Inc., Centre Eugene Marquis., Oncology, University of Surrey., Urology, UCLA School of Medicine., Urology, Spire Roding Hospital., Clinical Research Oncology, Pfizer Italia S.r.l., Medical Oncology, Hopital Saint-Andre, University Hospital.

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