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Re-challenge with catumaxomab in patients with malignant ascites: results from the SECIMAS study

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Abstract

Malignant ascites is a common phenomenon in cancer patients. It poses a great challenge to the clinician, because of limited treatment options and strong impairment of the quality of life of the often palliative patients. The SECIMAS study investigated the feasibility of a re-challenge with four catumaxomab intraperitoneal infusions in patients who had already received a first cycle of four infusions in the phase III CASIMAS study, which compared catumaxomab with and without prednisolone premedication. The primary endpoint was the proportion of patients who received at least three catumaxomab infusions. Secondary endpoints included a composite safety score (CSS) summarising the worst grades for the main catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain), safety, efficacy and the occurrence of anti-drug antibodies (ADAs). Eight of nine screened patients received a second catumaxomab cycle. Compliance with a catumaxomab re-challenge was high: all eight patients (100 %) received all four infusions. The median CSS was 3.0 versus 3.4 in CASIMAS. The tolerability profile of the second catumaxomab cycle was comparable to that of the first cycle. Median puncture-free survival (48 days) and overall survival (407 days) were longer than in CASIMAS (35 and 103 days, respectively), although median time to next puncture was shorter (60 vs. 97 days). Of six patients sampled, all were ADA positive at screening and remained ADA positive until the end of the study. The presence of ADAs did not affect catumaxomab’s safety or efficacy. The CSS and tolerability profile for catumaxomab in SECIMAS were comparable to those in CASIMAS. The majority of patients benefitted from a second cycle of catumaxomab. A re-challenge seems to be feasible and safe for selected patients with recurrent malignant ascites due to carcinoma after a first cycle of catumaxomab.

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Abbreviations

ADA:

Anti-drug antibody

CTCAE:

Common terminology criteria for adverse events

EpCAM:

Epithelial cell adhesion molecule

OS:

Overall survival

PuFS:

Puncture-free survival

TTPu:

Time to next puncture

VAS:

Visual analogue scale

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Acknowledgments

The study was sponsored by Neovii Biotech GmbH and supported by the North-Eastern German Society of Gynecology (NOGGO). The authors would like to thank the freelance medical writer Kevin De-Voy (funded by Fresenius Biotech GmbH) for his writing support.

Conflict of interest

Holger Martinius and Hilke Friccius-Quecke are employees of Neovii Biotech GmbH (formerly Fresenius Biotech GmbH). Klaus Pietzner has received honoraria for scientific presentations. All other authors report no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, European Competence Center for Ovarian Cancer, Charité-University Medicine of Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Klaus Pietzner, Radoslav Chekerov & Jalid Sehouli

  2. University Hospitals Leuven and Leuven Cancer Institute, Louvain, Belgium

    Ignace Vergote

  3. Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Italy

    Armando Santoro

  4. Nationales Centrum für Tumorerkrankungen (NCT), Universitätsfrauenklinik Heidelberg, heidelberg, Germany

    Frederik Marmé

  5. University Hospital Linköping, Linköping, Sweden

    Per Rosenberg

  6. Neovii Biotech GmbH, Munich, Germany

    Holger Martinius & Hilke Friccius-Quecke

  7. North-Eastern German Society of Gynecology (NOGGO), Berlin, Germany

    Jalid Sehouli

Authors
  1. Klaus Pietzner
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  2. Ignace Vergote
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  3. Armando Santoro
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  4. Radoslav Chekerov
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  5. Frederik Marmé
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  6. Per Rosenberg
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  7. Holger Martinius
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  8. Hilke Friccius-Quecke
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  9. Jalid Sehouli
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Corresponding author

Correspondence to Klaus Pietzner.

Additional information

Novelty and impact of the work Due to its murine nature, catumaxomab is highly immunogenic and induces anti-drug antibodies (ADAs). However, its safety and efficacy may not be compromised by ADAs. This study shows that compliance with a second cycle is high and that the presence of ADAs did not affect either the safety or efficacy of catumaxomab. A re-challenge seems to be safe and feasible for selected patients with recurrent malignant ascites due to carcinoma after a first cycle of catumaxomab.

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Pietzner, K., Vergote, I., Santoro, A. et al. Re-challenge with catumaxomab in patients with malignant ascites: results from the SECIMAS study. Med Oncol 31, 308 (2014). https://doi.org/10.1007/s12032-014-0308-x

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  • DOI: https://doi.org/10.1007/s12032-014-0308-x

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