real world experience with sunitinib treatment in patients with metastatic renal cell carcinoma clinical outcome according to risk score

Abstract Background ADONIS is an ongoing observational study in 9 European countries, designed to evaluate treatment patterns/outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with first-line sunitinib and/or second-line axitinib post sunitinib. We present an evaluation of sunitinib efficacy by risk group, in the real-world setting examined in ADONIS. Methods Patients were enrolled at the start of first-line sunitinib treatment or second-line axitinib post sunitinib treatment. Evaluation of sunitinib efficacy was assessed by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center risk criteria. Results For all patients in this analysis (N = 467), median progression-free survival was 23.8 (95% CI 16.5-28.5), 11.8 (8.1-17.4), and 4.6 (2.5-7.7) months for IMDC favorable-, intermediate-, and poor-risk groups, respectively. Median overall survival was 97.1 (46.3-not evaluable [NE]), 33.5 (20.5-46.6), and 10.0 (4.5-19.8) months for the respective risk groups. Data on individual risk factors were available for a subgroup of patients, allowing analysis by intermediate risk by 1 versus 2 risk factors. When including this subgroup (n = 120), median overall survival for IMDC favorable-, intermediate-1, and intermediate-2 risk factors was 21.6 (16.3-NE), 20.5 (15.5-NE), and 15.1 (4.1-NE) months, respectively. Conclusions For patients overall and by risk-group stratification, survival estimates were aligned with improvements in clinical practice over the past decade. In patients with intermediate-1 risk, overall survival was very similar to patients with favorable risk. However, further exploration is needed to confirm these observations. ClinicalTrials.gov identifier: NCT0218441

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

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.</p