Malignant
ascites is a common manifestation of advanced
cancers, and treatment options are limited. The trifunctional antibody
catumaxomab (anti-
epithelial cell-adhesion molecule x anti-CD3) represents a targeted
immunotherapy for the intraperitoneal (i.p.) treatment of malignant
ascites secondary to epithelial
cancers. In this phase II/III trial (EudraCT 2004-000723-15; NCT00836654),
cancer patients (n = 258) with recurrent symptomatic malignant
ascites resistant to conventional
chemotherapy were randomized to paracentesis plus
catumaxomab (
catumaxomab) or paracentesis alone (control) and stratified by
cancer type (129 ovarian and 129 nonovarian).
Catumaxomab was administered as an i.p. infusion on Days 0, 3, 7 and 10 at doses of 10, 20, 50 and 150 mug, respectively. The primary efficacy endpoint was
puncture-free survival. Secondary efficacy parameters included time to next paracentesis,
ascites signs and symptoms and overall survival (OS).
Puncture-free survival was significantly longer in the
catumaxomab group (median 46 days) than the control group (median 11 days) (hazard ratio = 0.254: p < 0.0001) as was median time to next paracentesis (77 versus 13 days; p < 0.0001). In addition,
catumaxomab patients had fewer signs and symptoms of
ascites than control patients. OS showed a positive trend for the
catumaxomab group and, in a prospectively planned analysis, was significantly prolonged in patients with
gastric cancer (n = 66; 71 versus 44 days; p = 0.0313). Although adverse events associated with
catumaxomab were frequent, they were manageable, generally reversible and mainly related to its immunologic mode of action.
Catumaxomab showed a clear clinical benefit in patients with malignant
ascites secondary to epithelial
cancers, especially
gastric cancer, with an acceptable safety profile.