Decrease of VEGF within malignant ascites during catumaxomab treatment: Results from a pivotal phase II/III study

Abstract

3029 Background: Treatment with the trifunctional anti-EpCAM x anti-CD3 antibody catumaxomab efficiently eliminates tumor cells from the peritoneal cavity (Jäger et al., ASCO 2007) and led to clinically relevant prolongation of puncture-free survival (PuFS) in patients with malignant ascites (MA) in a pivotal phase II/III trial (Parsons et al., ASCO 2008). As vascular endothelial growth factor (VEGF) levels are markedly elevated in MA in comparison to cirrhotic ascites the question was addressed whether catumaxomab treatment impacts the expression or accumulation of VEGF within MA. Here we report that in addition to tumor cell depletion, VEGF protein levels in MA significantly decreased upon catumaxomab therapy. We propose that the strongly correlated tumor cell elimination and reduced VEGF protein levels are causative for the prolonged PuFS of patients suffering from MA. Methods: VEGF and total protein levels were measured by ELISA and BCA from MA supernatants before catumaxomab therapy, after the 1st infusion (10μg; day 3) and after the 4th infusion (150μg; day 11). Data were statistically analysed for the ratio of the VEGF protein concentration versus the total protein concentration for the MA treatment groups with ovarian (OC) or nonovarian cancer (NC) as underlying disease and the corresponding control groups that received paracentesis only. Results: One day after the last catumaxomab infusion 46 or 47 patients analysed in the OC or NC treatment group showed a statistically significant decrease in VEGF to total protein ratio when compared to the measurement before catumaxomab therapy (ANOVA p=0.034 for OC and p<0.001 for NC). These results are consistent with the tumor cell elimination previously assessed in these patients. In contrast, the OC control group showed a statistically significant increase of VEGF to total protein ratio (p=0.009), which is accompanied by an increase in tumor cell numbers. In the NC control group VEGF to total protein ratio remained unaffected (p=0.096). Conclusions: Catumaxomab therapy significantly reduced VEGF protein levels correlating with tumor cell elimination in MA, which in turn led to the prevention of fluid accumulation in the peritoneal cavity and finally to prolonged PuFS of patients suffering from MA. [Table: see text]