Randomised phase II trial to investigate catumaxomab (anti-EpCAM × anti-CD3) for treatment of peritoneal carcinomatosis in patients with gastric cancer.

Abstract

BACKGROUND:

Peritoneal carcinomatosis (PC) represents an unfavourable prognostic factor for patients with gastric cancer (GC). Intraperitoneal treatment with the bispecific and trifunctional antibody catumaxomab (EpCAM, CD3), in addition to systemic chemotherapy, could improve elimination of PC.

METHODS:

This prospective, randomised, phase II study investigated the efficacy of catumaxomab followed by chemotherapy (arm A, 5-fluorouracil, leucovorin, oxaliplatin, docetaxel, FLOT) or FLOT alone (arm B) in patients with GC and PC. Primary endpoint was the rate of macroscopic complete remission (mCR) of PC at the time of second diagnostic laparoscopy/laparotomy prior to optional surgery.

RESULTS:

Median follow-up was 52 months. Out of 35 patients screened, 15 were allocated to arm A and 16 to arm B. mCR rate was 27% in arm A and 19% in arm B (p = 0.69). Severe side effects associated with catumaxomab were nausea, infection, abdominal pain, and elevated liver enzymes. Median progression-free (6.7 vs. 5.4 months, p = 0.71) and overall survival (13.2 vs. 13.0 months, p = 0.97) were not significantly different in both treatment arms.

CONCLUSIONS:

Addition of catumaxomab to systemic chemotherapy was feasible and tolerable in advanced GC. Although the primary endpoint could not be demonstrated, results are promising for future investigations integrating intraperitoneal immunotherapy into a multimodal treatment strategy.

• Authors: Maren Knödler, Justus Körfer, Volker Kunzmann, Jörg Trojan, Severin Daum, Michael Schenk, Frank Kullmann, Sebastian Schroll, Dirk Behringer, Michael Stahl, Salah-Eddin Al-Batran, Ulrich Hacker, Stefan Ibach, Horst Lindhofer, Florian Lordick
• Journal: British journal of cancer (Br J Cancer) Vol. 119 Issue 3 Pg. 296-302 (08 2018) ISSN: 1532-1827 [Electronic] England
• PMID: 29988111 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bispecific
• CD3 Complex
• EPCAM protein, human
• Epithelial Cell Adhesion Molecule
• Oxaliplatin
• Docetaxel
• catumaxomab
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Antibodies, Bispecific (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• CD3 Complex (antagonists & inhibitors, genetics)
• Docetaxel (administration & dosage)
• Epithelial Cell Adhesion Molecule (antagonists & inhibitors, genetics)
• Female
• Fluorouracil (administration & dosage)
• Gastrectomy
• Humans
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Neoplasm Metastasis
• Oxaliplatin (administration & dosage)
• Peritoneal Neoplasms (drug therapy, genetics, secondary, surgery)
• Stomach Neoplasms (drug therapy, genetics, pathology)