The effect of low serum sodium on treatment outcome to vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma: Results from a large international collaboration.

Abstract

322 Background: Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients (pts) treated with immunotherapy (Jeppesen et al, Br J Cancer. 2010). We sought to investigate the influence of baseline hyponatremia in mRCC pts treated with contemporary vascular endothelial growth factor (VEGF)- targeted therapy in a larger international and multi-institutional database. Methods: Baseline characteristics and outcomes on 855 pts treated with first-line anti-VEGF therapy for mRCC were available from 8 Cancer Centers to study the impact of hyponatremia (defined as serum Na<135 mmol/L) on clinical outcome as measured by overall survival (OS), time to treatment failure (TTF), best response (CR, PR, SD and PD). Results: Median OS after treatment initiation was 16.8 months (mos) (95% CI: 14.9, 18.5 mos), with 334 (39%) of patients remaining alive. Median follow-up in pts alive was 18.8 mos. Median baseline serum sodium was 138 mmol/L (range: 122–159), and hyponatremia was found in 16.7% of pts. On univariate analysis, hyponatremia was associated with shorter OS (6.5 vs. 18.8 mos; HR 2.32 [95% CI: 1.86–2.89], p<0.0001), shorter TTF (2.8 vs. 6.9 mos.; HR 2.20 [95% CI: 1.81–2.68], p<0.0001), and lower disease control rate (DCR) as defined by CR+PR+SD (51.2% vs. 74.6%, OR 0.36 [95% CI: 0.2–0.57], p<0.0001). In multivariate analysis adjusted for MSKCC or Heng's risk criteria (JCO 2009), these effects remain significant with p<0.001 for OS and TTF and p=0.01 for DCR. The results were similar (p<0.001) if sodium was analyzed as a continuous variable. Conclusions: This is the first large multi-institutional report to show that low serum sodium is independently associated with a worse outcome in mRCC pts treated with VEGF-targeted agents. No significant financial relationships to disclose.