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

George, D, Martini, J-F, Staehler, M, Motzer, R, Magheli, A, Escudier, B, Gerletti, P, Li, S, Casey, M, Laguerre, B , Pandha, Hardev, Pantuck, A, Patel, A, Lechuga, M and Ravaud, A (2018) Immune biomarkers predictive for disease-free survival with adjuvant sunitinib in high-risk locoregional renal cell carcinoma: from randomized phase III S-TRAC study Clinical Cancer Research.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
George, DUNSPECIFIEDUNSPECIFIED
Martini, J-FUNSPECIFIEDUNSPECIFIED
Staehler, MUNSPECIFIEDUNSPECIFIED
Motzer, RUNSPECIFIEDUNSPECIFIED
Magheli, AUNSPECIFIEDUNSPECIFIED
Escudier, BUNSPECIFIEDUNSPECIFIED
Gerletti, PUNSPECIFIEDUNSPECIFIED
Li, SUNSPECIFIEDUNSPECIFIED
Casey, MUNSPECIFIEDUNSPECIFIED
Laguerre, BUNSPECIFIEDUNSPECIFIED
Pandha, HardevH.Pandha@surrey.ac.ukUNSPECIFIED
Pantuck, AUNSPECIFIEDUNSPECIFIED
Patel, AUNSPECIFIEDUNSPECIFIED
Lechuga, MUNSPECIFIEDUNSPECIFIED
Ravaud, AUNSPECIFIEDUNSPECIFIED
Date : 26 January 2018
Identification Number : 10.1158/1078-0432.CCR-17-2822
Copyright Disclaimer : Copyright ©2018, American Association for Cancer Research.
Related URLs :
Depositing User : Melanie Hughes
Date Deposited : 31 Jan 2018 14:53
Last Modified : 31 Jan 2018 15:22
URI: http://epubs.surrey.ac.uk/id/eprint/845718

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