This randomized, double-blind phase 3 trial examined the efficacy and safety of SU vs PBO in post-nephrectomy patients (pts) with locoregional RCC at high risk (per modified UISS criteria) of tumor recurrence.
Treatment-naïve pts (n = 615) with locoregional RCC (≥T3 and/or N1–2) received 50 mg/d SU or PBO in a 4-wks-on/2-wks-off schedule for 1 yr until disease recurrence, occurrence of secondary malignancy, significant toxicity, or consent withdrawal. One dose reduction to 37.5 mg/d was allowed. Baseline imaging was centrally reviewed to exclude pts with suspicion of metastases. Primary endpoint was disease-free survival (DFS) assessed by central review. Secondary endpoints included investigator-assessed DFS, overall survival (OS), safety, and pt-reported outcomes.
Baseline characteristics were balanced between the SU (n = 309) and PBO (n = 306) arms. Median (m) number of cycles and relative dose intensity (SU) were 9 and 88.4%, respectively. Fewer DFS events were seen with SU (113; 36.6%) vs PBO (144; 47.1%). The trial met its primary endpoint: DFS by central review was significantly longer for SU vs PBO (HR, 0.761; P = 0.030), and these results were supported by secondary DFS analyses in all randomized pts and a higher-risk subgroup (Table 1). OS data were immature at data cutoff (mOS not reached in either arm). Grade ≥3 adverse events (AEs) were more frequent with SU (62.1%) vs PBO (21.1%), but serious AE incidence was similar (21.9% vs 17.1%); no death occurred due to treatment toxicity.
|SU||PBO||HR (95% CI) SU vs. PBO||P|
|mDFS (95% CI) (yr)|
|All randomized||6.8 (5.8–NR)||5.6 (3.8–6.6)||0.761 (0.594–0.975)||0.030|
|Higher-risk*||6.2 (4.9–NR)||4.0 (2.6–6.0)||0.737 (0.548-0.993)||0.044|
|All randomized||6.5 (4.7–7.0)||4.5 (3.8–5.9)||0.811 (0.643–1.023)||0.077|
|Higher-risk*||5.9 (4.4–7.0)||3.9 (2.8–5.6)||0.763 (0.577–1.009)||0.056|
* T3, N0 or NX, M0, Fuhrman's grade ≥2, ECOG PS ≥1 and T4 and/or N1–2
SU prolonged DFS in pts with locoregional RCC at high risk for recurrence. Given the increase in DFS and the manageable safety profile, SU represents a potential new treatment option as adjuvant therapy in RCC.
Clinical trial identification
NCT00375674 (Release date: July 2016)
Legal entity responsible for the study
A. Ravaud: Member of advisory boards in RCC for Pfizer, Novartis, GSK, Roche, and BMS, and received institutional support grants from Pfizer and Novartis, and housing and transportation for meetings and speeches by Pfizer, Novartis, and BMS. R.J. Motzer: received personal fees and other from Pfizer, Eisai, Novartis, and Exelixis, and other from Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, and Acceleron. M. Staehler: received honoraria, consulting fees, and research grants from Pfizer, Bayer, Novartis, Roche, Bristol Myers Squibb, Aveo, GSK, and Exelixis, and consulting fees from Eisai. D. George: reports honoraria & consulting: Dendreon, Sanofi, Novartis, Bayer; consulting: Medivation, Merck, Genentech; grants: Genentech/Roche, Novartis, Janssen, Astellas, Celldex, Acerta; grants & consulting: Exelixis, Pfizer, Sanofi, Innocrin Pharma, BMS. A.J. Pantuck, A. Patel: received consulting fees from Pfizer. B. Escudier: Received consulting fees from Bayer, Pfizer, and Novartis, and honoraria from Bayer, Roche, Pfizer, Genentech, Novartis, and Aveo. F. Donskov: Received research funding from Pfizer, Novartis, and GSK. A. Magheli: Received compensations for speeches from Janssen, Bayer, Astellas, and Pfizer. B. Laguerre: Received honoraria from Pfizer. P. Gerletti, X. Lin, M. Lechuga, J-F. Martini: Is an employee of and owns stock in Pfizer Inc. J-J. Patard: received consulting fees from Pfizer and GSK. All other authors have declared no conflicts of interest.