Treatment of epithelial cancer patients with malignant ascites using catumaxomab: Results of the non-ovarian stratum of a phase II/III study

Introduction: Malignant ascites (MA) in patients (pts) with epithelial cancer is associated with a poor prognosis and reduced quality of life. Catumaxomab (catu) is known to simultaneously activate T cells and FcG-receptor pos. cells and to redirect them against the tumor (TU). Pts were analyzed in two strata: ovarian and non-ovarian cancer pts. These are the results of the non-ovarian stratum. Methods: A total of 129 non-ovarian cancer pts with recurrent MA containing EpCAM+ TU cells were enrolled in the study; 85 were randomized to treatment with catu (paracentesis plus intraperitoneal [ip] infusion of 10, 20, 50 and 150 µg within 11 days [d]), and 44 d to the control arm (paracentesis alone). The primary endpoint was puncture free survival (PFS) (time to first need for paracentesis after treatment or time to death, which ever occurred first). Results: Pts characteristics were well balanced in both arms. Gastric cancer (GC) pts were the largest subgroup (51.2 %). Median PFS was 37 d for catu vs. 14 d for control (GC 44 d vs. 15 d) (both p<0.0001), the median time to next paracentesis was 80 d vs. 15 d (GC 118 d vs. 15 d) (both p<0.0001). The Time to Progression (TTP) was also significant prolonged (all pts 110 d vs 34 d; GC 110 d vs 35 d; both p<0.0001). The positive trend was also observed for overall survival (OS); for the GC pts a significant difference was seen (71 d vs. 44 d, p=0.0313). The most frequent AEs were symptoms related to cytokine release (pyrexia, nausea, vomiting). These were generally mild to moderate, and fully reversible. Transient increases in liver enzymes and bilirubin, and transient WBC abnormalities such as leukocytosis, neutrophilia and a decrease in peripheral lymphocytes were regularly observed as abnormal laboratory values but rarely considered clinically significant. 80.5% pts received all 4 catu doses. Conclusions: Intraperitoneal therapy with catu resulted in a significant and clinically relevant improvement of PFS time, and time to next puncture compared to the control group. Prolonged TTP and OS indicate effects on the underlying TU. GC patients benefited most from catu. The safety profile reflects catu`s mode of action and reveals a low and acceptable toxicity.