The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial.

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.

XM02, the first biosimilar G-CSF, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with small cell or non-small cell lung cancer receiving platinum-based chemotherapy.

BACKGROUND: Recombinant granulocyte colony-stimulating factors such as Neupogen are used to treat chemotherapy-induced neutropenia. The aim of the study was to show that a new granulocyte colony-stimulating factor, XM02, is as safe and effective as Neupogen in the treatment of chemotherapy-induced neutropenia in patients with small cell or non-small cell lung cancer. PATIENTS AND METHODS: A total of 240 patients receiving platinum-based chemotherapy were randomized in cycle 1 to treatment with daily injections (subcutaneous 5 microg/kg/d) of XM02 (n = 160) or Filgrastim Neupogen (n = 80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received XM02. RESULTS: The mean duration of severe neutropenia was 0.5 and 0.3 days in cycle 1 for XM02 and Filgrastim, respectively. In the analysis of covariance for duration of severe neutropenia in cycle 1, the estimated treatment difference "XM02 minus Filgrastim" was 0.157 days, with 95% confidence level (-0.114 days, 0.428 days), which was included in the prespecified equivalence range (-1, 1). There was no statistically significant difference of the end point incidence of febrile neutropenia in cycle 1 between XM02 and Filgrastim (p = 0.2347). The adverse event profile was similar between XM02 and Filgrastim. CONCLUSION: XM02 demonstrated similar efficacy and safety profile as the reference medication Filgrastim in cycle 1. In conclusion, treatment with XM02 is beneficial in ameliorating severe neutropenia and febrile neutropenia in lung cancer patients receiving myelosuppressive chemotherapy. XM02 is safe and well tolerated in the doses applied in this study.