Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results

Abstract

Background: Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03).

Objective: To report the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS).

Design, setting, and participants: Data for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial.

Outcome measurements and statistical analysis: Subgroup DFS analyses by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio (NLR), and Fuhrman grade.

Results and limitations: Of 615 patients, 97 and 122 in the sunitinib and placebo arms developed metastatic disease, with the most common sites of distant recurrence being lung (40 and 49), lymph node (21 and 26), and liver (11 and 14), respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively.

Conclusions: A benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy.

Patient summary: Most subgroups of patients at high risk of recurrent renal cell carcinoma after nephrectomy experienced a clinical benefit with adjuvant sunitinib.

Trial registration: ClinicalTrials.gov NCT00375674.

Keywords: Adjuvant; Disease-free survival; Renal cell carcinoma; Sunitinib.

Fig. 1 –

Disease-free survival by subgroup. * T3 tumor, no or undetermined nodal involvement, no metastasis, any Fuhrman grade, ECOG PS 0; or Fuhrman grade 1, ECOG PS 1. ^† T3 tumor, no or undetermined nodal involvement, no metastasis, Fuhrman grade ≥2, ECOG PS ≥1. ^‡ T4 tumor or any T stage with nodal involvement, no metastasis, any Fuhrman grade, any ECOG PS. BMI = body mass index; CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group performance status; HR = hazard ratio; NLR = neutrophil-to-lymphocyte ratio; UISS = University of California Los Angeles integrated staging system.

Fig. 2 –

Disease-Free survival in patients at higher risk according to blinded independent central review. Higher risk was defined as T3, no or undetermined nodal involvement, no metastasis, Fuhrman grade ≥2, ECOG PS ≥1; or T4 and/or nodal involvement. CI = confidence interval; HR = hazard ratio; DFS = disease-free survival; NR = not reached.

Fig. 3 –

Kaplan-Meier estimates of overall survival (OS) in the intent-to-treat population. * Two-sided p value from log-rank test stratified by University of California, Los Angeles integrated staging system high-risk group: T3 or T4, no or undetermined nodal involvement, no metastasis, or any T stage with local nodal involvement, and for all patients, any Fuhrman grade and any Eastern Cooperative Oncology Group performance status. CI = confidence interval; ECOG PS =; HR = hazard ratio; NR = not reached.