Influence of risk factors for renal cell carcinoma (RCC) on outcome of patients (pts) with metastatic disease treated with sunitinib.

Abstract

437 Background: Obesity, smoking, hypertension (HTN) and diabetes (DM) are risk factors for RCC development. Their presence has been associated with a worse outcome of therapy (tx) in various metastatic cancers. We sought to determine their influence on the progression free survival (PFS) and overall survival (OS) of Su tx in mRCC. Methods: We performed a multicentre retrospective study of pts with mRCC, who were treated with Su. We analyzed the pre-tx status of smoking (active vs past vs never), BMI (obese=BMI≥30 vs overweight=BMI 25-29.9 vs normal weight=BMI <25), HTN, DM, and known prognostic factors including past nephrectomy, clear cell/non clear cell histology, time from initial diagnosis to Su tx, > 2 metastasis (mets) sites, lung/liver/bone mets, ECOG performance status, anemia, calcium level > 10 mg/dL, elevated alkaline phosphatase (AP), platelets count, pre-tx neutrophil to lymphocyte ratio (NLR) >3, Su induced HTN, use of angiotensin system inhibitors (ASIs), past cytokines/targeted tx, and mean Su dose/cycle. PFS and OS were determined by the Kaplan-Meier method. Multivariate analyses using Cox Regression model were performed to determine their independent effect. Results: Between 2004-2011, 209 pts with mRCC were treated with Su. 40 pts were active smoker, 51 obese, 55 diabetic, and 122 had pre-tx HTN. In the entire pt cohort, median PFS was 8 months (mos) and OS 15 mos. Factors associated with PFS were active smoking (HR 2.5, p= 0.005, median PFS 4 vs 10 mos in past smokers vs 10 mos in never smokers), non clear cell histology (HR 1.8, p=0.023), pre-tx NLR >3 (HR 0.2, p<0.0001) and the use of ASIs (HR 1.66, p=0.028). Factors associated with OS were were active smoking (HR 2.1, p= 0.03, median OS 8.5 vs 18 mos in past smokers vs 18 mos in never smokers), AP (HR 1.76, p=0.049), pre-tx NLR >3 (HR 0.294, p<0.0001), and liver mets (HR 0.553, p=0.04). BMI, DM, and pre-tx HTN were not associated with PFS or OS. Conclusions: Active smoking may decrease the PFS and OS of pts with mRCC that are treated with Su. BMI, DM, and pre-tx HTN were not found to be associated with outcome. These results should be investigated prospectively, and if validated applied in clinical practice and clinical trials.