ASCO 2017: Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma (RCC): Validation of the 16-gene Recurrence Score in stage III patients

Chicago, IL ( In the last year, the S-TRAC randomized controlled trial (RCT) [1] demonstrated that patients receiving adjuvant sunitinib vs placebo for high risk renal cell carcinoma (RCC) have improved disease-free survival (DFS). Similarly, at the same session this morning, it was reported that patients treated with adjuvant pazopanib (800 mg) may also have improved DFS [2]. However, selecting which patients may benefit from adjuvant treatment has been largely unknown. Dr. Escudier and colleagues presented their results of a 16-gene Recurrence Score for stage III RCC patients to further characterize which patients may benefit from adjuvant therapy at today’s ASCO 2017 annual meeting genitourinary cancer oral abstract session. The 16-gene Recurrence Score was previously developed and validated to predict risk of recurrence of RCC after nephrectomy in 2 cohorts of stage I–III pts [3]. The objective of this study was to present further validation of the Recurrence Score in high-risk stage III patients from S-TRAC.

This study was prospectively designed with prespecified genes and analysis plan using primary RCC tissues from 193 stage III evaluable patients from S-TRAC. Gene expression was quantitated using RT-PCR, and time to recurrence (TTR) and DFS were analyzed using Cox proportional hazards modelling. Baseline characteristics were similar in sunitinib and placebo arms and in patients with and without gene expression data. The Recurrence Score predicted TTR (HR 2.5-4.2) and DFS (HR 2.3-3.8) in both the treatment and placebo arms, with stronger results noted in the placebo arm. The authors also note that the interaction of Recurrence Score with treatment was not significant (TTR p=0.19; DFS p=0.22); however, the number of events was relatively low.

In conclusion, the prognostic value of the Recurrence Score gene assay was confirmed in the high-risk stage III S-TRAC patients, with the strongest association observed in the placebo arm. Since the Recurrence Score has now been validated in multiple studies, these results may help identify patients at high-risk who may derive added benefit from adjuvant therapy. Given the side effect incidence and severity in the previous RCTs with adjuvant treatment, having additional predictors selecting patients that may benefit from adjuvant therapy is significant.

Presented By: Bernard J. Escudier, Gustave Roussy Cancer Campus, Paris, France

Co-Authors: Brian I. Rini, Jean-Francois Martini, Wayne Yen-Hwa Chang, Jan Breza, Ahmed Magheli, Christer Svedman, Margarita Lopatin, Dejan Knezevic, Audrey D. Goddard, Patricia A English, Rachel Li, Xun Lin, Olga Valota, Giacomo Cartenì, Michael D. Staehler, Robert J. Motzer, Alain Ravaud

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA

1. Ravaud A, Motzer RJ, Pandha HS, et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med 2016 Dec 8;375(23):2246-2254.
2. Motzer RJ, Haas NB, Donskov F, et al. Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with locally advanced renal cell carcinoma (RCC) (PROTECT). J Clin Oncol 2017;35(suppl; abstr 4507).
3. Rini B, Goddard A, Knezevic D, et al. A 16-gene assay to predict recurrence after surgery in localized renal cell carcinoma: development and validation studies. Lancet Oncol 2015 Jun;16(6):676-685.