Validation of the 16-Gene Recurrence Score in patients with locoregional, high-risk renal cell carcinoma from a phase 3 trial of adjuvant sunitinib

Adjuvant sunitinib prolonged disease-free survival (DFS) (hazard ratio [HR] 0.76) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov NCT00375674). The 16-gene Recurrence Score (RS) assay was previously developed and validated to estimate risk for disease recurrence in patients with RCC post-nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored association of RS results with prediction of sunitinib benefit.

The analysis was prospectively designed with prespecified genes, algorithm, endpoints, and analytical methods. Primary RCC was available from 212 patients with informed consent; primary analysis focused on patients with T3 RCC. Gene expression was quantitated by RT-PCR. Time to recurrence (TTR), DFS, and renal cancer-specific survival (RCSS) were analyzed using Cox proportional hazards regression. Results: Baseline characteristics were similar between patients with and without RS results, and between the sunitinib and placebo arms among patients with RS results. RS results predicted TTR, DFS, and RCSS in both arms, with the strongest results observed in the placebo arm. When high versus low RS groups were compared, HR for recurrence was 9.18 (95% CI, 2.15-39.24; P < 0.001) in the placebo arm; interaction of RS results with treatment was not significant. Conclusions: The strong prognostic performance of the 16-gene RS assay was confirmed in S-TRAC, and the RS assay is now supported by level IB evidence. RS results may help identify patients at high risk for recurrence who may derive higher absolute benefit from adjuvant therapy.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2018 May 17 [Epub ahead of print]

Brian I Rini, Bernard Escudier, Jean-Francois Martini, Ahmed Magheli, Christer Svedman, Margarita Lopatin, Dejan Knezevic, Audrey D Goddard, Phillip G Febbo, Rachel Li, Xun Lin, Olga Valota, Michael Staehler, Robert J Motzer, Alain Ravaud

Hematology/Oncology, Cleveland Clinic Taussig Cancer Institute ., Gustave-Roussy., Translational Oncology, Pfizer Inc., Charité Universitaetsmedizin Berlin., Genomic Health Inc., Development, Genomic Health (United States)., Biomarker & Assay Development, Omniox Inc., Chief Medical Officer, Genomic Health, Inc., Pfizer Inc., Statistics, Pfizer Oncology., Cell Biology, Nerviano Medical Sciences srl., Hospital of Munich., Department of Medicine, Memorial Sloan Kettering Cancer Center., Medical Oncology, Hopital Saint-Andre, University Hospital.

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