Validation of the 16-Gene Recurrence Score in Patients with Locoregional, High-Risk Renal Cell Carcinoma from a Phase III Trial of Adjuvant Sunitinib

Abstract

Adjuvant sunitinib prolonged disease-free survival (DFS; 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 after nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored the 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. Baseline characteristics were similar between patients with and those 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% confidence interval (CI), 2.15-39.24; < 0.001) in the placebo arm; interaction of RS results with treatment was not significant. 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. .

Update on the Biology and Management of Renal Cell Carcinoma

“…Additionally, a study has reported the validation of a 16-gene recurrence score for RCC using the subjects of the S-TRAC trial 123. This will likely be evaluated in all ongoing trials in which tissue is available for analysis.…”

Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor of Disease-free Survival in Postnephrectomy High-risk Locoregional Renal Cell Carcinoma: Analysis of the S-TRAC Trial

“…A prospectively designed analysis of immune tissue biomarkers in the S-TRAC trial population reported that a greater CD8 þ T-cell density in tumor tissue was associated with a longer DFS in patients who received sunitinib (24). A validated 16-gene recurrence score (RS) assay, developed to predict the likelihood of recurrence postnephrectomy in patients with locoregional RCC (25), was further validated in a prospectively designed analysis of the S-TRAC population (26). The RS successfully predicted time to recurrence, DFS, and renal cancer-specific survival in both placebo and sunitinib arms (26).…”

“…A validated 16-gene recurrence score (RS) assay, developed to predict the likelihood of recurrence postnephrectomy in patients with locoregional RCC (25), was further validated in a prospectively designed analysis of the S-TRAC population (26). The RS successfully predicted time to recurrence, DFS, and renal cancer-specific survival in both placebo and sunitinib arms (26). In addition, a pharmacogenomic analysis of the S-TRAC trial found that SNPs in the VEGFR1 and VEGFR2 genes were associated with longer DFS in patients receiving adjuvant sunitinib (27).…”

Adjuvant therapy for high‐risk renal cell carcinoma after nephrectomy how many trials are positive? Only one or more than one

“…Better selection of patients to establish a more accurate knowledge of risk has been approached by tumor and stroma signature, including a 34‐gene subtype predictor to classify clear cell renal carcinoma tumours according to ccA (good risk) and ccB (poor risk) subtypes, and a 16‐gene assay for calculating a recurrence score to predict recurrence after surgery, but are not part of ongoing trials.…”