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Catumaxomab with and without prednisolone premedication for the treatment of malignant ascites due to epithelial cancer: results of the randomised phase IIIb CASIMAS study

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Abstract

This two-arm, randomised, multicentre, open-label, phase IIIb study investigated the safety and efficacy of a 3-h catumaxomab infusion with/without prednisolone premedication to reduce catumaxomab-related adverse events. Patients with malignant ascites due to epithelial cancer received four 3-h intraperitoneal catumaxomab infusions with/without intravenous prednisolone (25 mg) premedication before each infusion. The primary safety endpoint was a composite safety score calculated from the incidence and intensity of the most frequent catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain). Puncture-free survival (PuFS) was a co-primary endpoint. Time to next puncture (TTPu) and overall survival (OS) were secondary endpoints. Prednisolone premedication did not result in a significant reduction in the main catumaxomab-related adverse events. The mean composite safety score was comparable in both arms (catumaxomab plus prednisolone, 4.1; catumaxomab, 3.8; p = 0.383). Median PuFS (30 vs. 37 days) and TTPu (78 vs. 102 days) were shorter in the catumaxomab plus prednisolone arm than in the catumaxomab arm, but the differences were not statistically significant (p = 0.402 and 0.599, respectively). Median OS was longer in the catumaxomab plus prednisolone arm than in the catumaxomab arm (124 vs. 86 days), but the difference was not statistically significant (p = 0.186). The superiority of catumaxomab plus prednisolone versus catumaxomab alone could not be proven for the primary endpoint. Prednisolone did not result in a significant reduction in the main catumaxomab-related adverse events. The study confirms the safety and efficacy of catumaxomab administered as four 3-h intraperitoneal infusions for the treatment of malignant ascites.

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Abbreviations

CASIMAS:

Catumaxomab safety with intraperitoneal infusion in malignant ascites

EpCAM:

Epithelial cell-adhesion molecule

OS:

Overall survival

PuFS:

Puncture-free survival

QoL:

Quality of life

TTPu:

Time to next puncture

ULN:

Upper limit of normal

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Acknowledgments

The authors would like to thank all the investigators who participated in the study: Dr. J. M. Aranda Lara, Cordoba, Spain; Prof. S. Barni, Treviglio, Italy; Dr. K. Baumann, Marburg, Germany; Dr. A. Block, Hamburg, Germany; Dr. V. Bondar, Donetsk, Ukraine; Prof. I. Bondarenko, Dnepropetrovsk, Ukraine; Dr. M. Candiani, Milan, Italy; Dr. A. Casado, Madrid, Spain; Dr. P. Chollet, Clermont-Ferrand, France; Prof. G. Colucci, Bari, Italy; Prof. P. Conte, Modena, Italy; Dr. T. Delaunoit, Haine St Paul, Belgium; Dr. J. M. del Campo, Barcelona, Spain; Dr. G. Demolin, Liege, Belgium; Dr. X. Durando, Clermont-Ferrand, France; Prof. A. Ferrari, Milan, Italy; Dr. E. François, Nice, France; Dr. A. Gambino, Brescia, Italy; Dr. A. Goncalves, Marseille, France; Dr. A. González del Alba, Palma, Majorca; Dr. A. González Martín, Madrid, Spain; Dr. J.-P. Guastalla, Lyon, France; Dr. E. Guerra Alía, Madrid, Spain; Dr. H. Havsteen, Herlev, Denmark; Prof. V. Heinemann, Munich, Germany; Dr. C. Kahl, Magdeburg, Germany; Dr. E. Kettner, Magdeburg, Germany; Dr. P. Klare, Berlin, Germany; Dr. S. Kubicka, Hannover, Germany; Prof. R. Labianca, Bergamo, Italy; Dr. R. Lopéz, Santiago de Compostela, Spain; Dr. S. Lorenzen, Heidelberg, Germany; Dr. D. Lüftner, Berlin, Germany; Dr. E. Luporsi, Nancy, France; Prof. A. Martoni, Bologna, Italy; Dr. B. Massuti, Alicante, Spain; Dr. K. Meunier, Angers, France; Prof. S. Pecorelli, Brescia, Italy; Dr. S. Pignata, Naples, Italy; Prof. P. Piso, Regensburg, Germany; Dr. E. Polycarpe, Angers, France; Dr. F. Popp, Regensburg, Germany; Dr. A. Poveda, Valencia, Spain; Dr. E. Rota Caremoli, Bergamo, Italy; Prof. G. Salerno, Pisa, Italy; Prof. B. Schmalfeldt, Munich, Germany; Dr. G. Schuch, Hamburg, Germany; Dr. E. Sevin, Caen, France; Prof. S. Siena, Milan, Italy; Dr. D. Spaeth, Nancy, France; Prof. M. Stahl, Essen, Germany; Dr. W. Stummvoll, Linz, Austria; Dr. H. Trum, Amsterdam, The Netherlands; Dr. W. M. Van Baal, Amsterdam, The Netherlands; Dr. F. Viret, Marseille, France and Dr. A. Vogel, Hannover, Germany. The authors would also like to thank the freelance medical writer Kevin De-Voy (funded by Fresenius Biotech GmbH) for his writing support.

Conflict of interest

Klaus Pietzner received honoraria for scientific lectures. Hilke Friccius-Quecke is employee of Neovii Biotech (former Fresenius Biotech). All other authors do not report a conflict of interest.

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Authors and Affiliations

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

    Jalid Sehouli & Klaus Pietzner

  2. Technische Universität Dresden, Dresden, Germany

    Pauline Wimberger

  3. Leuven Cancer Institute, University Hospitals Leuven, Louvain, Belgium

    Ignace Vergote

  4. University Hospital Linköping, Linköping, Sweden

    Per Rosenberg

  5. University Hospital Heidelberg, Heidelberg, Germany

    Andreas Schneeweiss

  6. University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Carsten Bokemeyer

  7. Hematology Oncology Clinic, Munich, Germany

    Christoph Salat

  8. Catholic University of Rome, Rome, Italy

    Giovanni Scambia

  9. CLCC René Gauducheau, Saint Herblain, France

    Dominique Berton-Rigaud

  10. Humanitas Cancer Center, Rozzano, Milan, Italy

    Armando Santoro

  11. Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain

    Andrés Cervantes

  12. Centre Léon Bérard, Lyon, France

    Olivier Trédan

  13. Hôpital Saint-Antoine, Paris, France

    Christophe Tournigand

  14. University of Milan-Bicocca, Milan, Italy

    Nicoletta Colombo

  15. Kharkov Medical Academy of Postgraduate Education, Kharkov, Ukraine

    Alexander S. Dudnichenko

  16. Academic Medical Center, Amsterdam, The Netherlands

    Anneke Westermann

  17. Neovii Biotech GmbH, Munich, Germany

    Hilke Friccius-Quecke

  18. University Cancer Center Leipzig, Leipzig, Germany

    Florian Lordick

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  1. Jalid Sehouli
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Correspondence to Klaus Pietzner.

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Jalid Sehouli and Klaus Pietzner have contributed equally to this article.

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Sehouli, J., Pietzner, K., Wimberger, P. et al. Catumaxomab with and without prednisolone premedication for the treatment of malignant ascites due to epithelial cancer: results of the randomised phase IIIb CASIMAS study. Med Oncol 31, 76 (2014). https://doi.org/10.1007/s12032-014-0076-7

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