Author(s): Berek JS, Edwards RP, Parker L, DeMars LR, Herzog TJ
Background: Malignant ascites (MA) in ovarian carcinoma (OC) patients (pts) is associated with a poor prognosis and reduced quality of life due to symptoms from ascites. In 2009, catumaxomab was approved in the EU for the intraperitoneal (IP) treatment of MA. Methods: In this single-arm, open-label, US, multicenter, phase II study, 32 chemotherapy-refractory and heavily pretreated (median of 4.5 prior chemotherapies) OC pts with MA were treated with catumaxomab. Pts received 4 IP infusions (10, 20, 50, and 150 µg) over 3 hours on days 0, 3, 7, and 10. The primary endpoint was the proportion of pts with at least a 4-fold increase in the puncture-free interval (PuFI) relative to their pretreatment interval. Main secondary endpoints were puncture-free survival (PuFS), overall survival (OS), MA symptoms based on patient-assessed FACIT-AI scores, safety, and tolerability. Results: 22.6% pts achieved at least a 4-fold increase in the PFI after catumaxomab treatment, which was below the predefined threshold of 60%. In median, the PFI was prolonged 2.0 fold in the full-analysis set (from median of 1.7 to 3.9 weeks) and 2.9 fold in the per-protocol set (from median of 2.6 to 7.1 weeks). 19 (59.4%) pts required paracentesis after catumaxomab treatment. The other pts died or were lost to follow up. The median PuFS was 4.2 weeks and median OS was 3.6 months. After catumaxomab treatment, patients’ symptoms improved in the majority of 13 predefined categories or remained stable. At repuncture, most symptoms were still improved compared with screening. The most frequent adverse events, pyrexia, nausea, and vomiting, are related to cytokine release. Transient increases in liver parameters and transient decreases in blood lymphocytes were regularly observed but were generally without clinical relevance. Conclusions: The study demonstrates an overall prolongation of PuFI and improvement of MA symptoms in these heavily pretreated patients. The median OS of 3.6 months support a therapeutic effect of catumaxomab. The safety profile of catumaxomab was acceptable, consistent with its mode of action and similar to that in previous clinical studies.