A phase II study of catumaxomab administered intra- and postoperatively as part of a multimodal approach in primarily resectable gastric cancer

Abstract

Background Postoperative relapse rate after gastrectomy and perioperative chemotherapy remain high in patients with advanced gastric cancer due to the spread of disseminated tumour cells in the peritoneal cavity. Perioperative administration of catumaxomab could potentially eliminate residual tumour cells after intended curative resection of the primary tumour. Methods This open-label, phase II study investigated the safety and efficacy of catumaxomab following neoadjuvant chemotherapy and subsequent surgery in patients with resectable (T2-4, N?, M0) gastric adenocarcinoma. Patients received catumaxomab intra-(single 10 lg dose) and postoperatively (10, 20, 50 and 150 lg on days 7, 10, 13 and 16, respectively). The primary endpoint was the postoperative complication rate (maximum rate defined as \62 %) within 30 days after surgery in patients who received at least the first catumaxomab dose.Results Of 64 patients treated with neoadjuvant chemotherapy, 58 underwent surgery and 54 received at least the first catumaxomab dose. Postoperative complications were reported in 18 of 54 evaluable patients (complication rate 33 %; 95 % confidence interval: 21-48 %); thus, the primary endpoint was met. The most frequent complications were pulmonary infection (17 %) and anastomosis insufficiency requiring surgery (11 %). The most common catumaxomab-related adverse events were pyrexia (67 %), leucocytosis (19 %), abdominal pain (17 %) and chills (17 %). The 4-year disease-free and overall survival rates were 38 and 50 %. Conclusion Intra-and postoperative administration of catumaxomab as part of a multimodal treatment approach was feasible and tolerable in patients with advanced gastric cancer and should be further investigated in a randomised trial.

Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis

“…Five of the nine patients also had stable or partial regression of disease, with a mean overall survival of 11.8 months, compared to a mean survival of 6 months in the EVOCAPE study by Sadeghi et al [ 91 , 95 ]. Catumaxomab has also been shown to have a tolerable toxicity profile in patients with resectable gastric cancer treated perioperatively [ 88 ]. Catumaxomab in combination with paracentesis can be effective in treating malignant ascites and improving the overall survival and quality of life of ovarian and gastric cancer patients [ 91 , 96 ].…”

Optimizing outcomes for patients with gastric cancer peritoneal carcinomatosis

“…In patients with malignant ascites from PC of gastric origin, it was found to significantly prolong OS from 44 to 71 d[ 45 ]. Bokemeyer et al[ 46 ] conducted a phase 2 study where patients underwent intra- and post-operative intraperitoneal catumaxomab administration after undergoing neoadjuvant chemotherapy and resection. These patients had four-year disease-free survival rates of 38% and four-year OS rates as high as 50%.…”

A unified model of the hierarchical and stochastic theories of gastric cancer

“…EpCAM has long been considered a potential target for antitumour therapy, and vaccination with EpCAM protein has been proposed (Mosolits et al , 2004). Furthermore, clinical trials of mAbs have ranged from testing the first murine IgG2a antibody, termed edrecolomab (Mosolits et al , 2004), to the EpCAM/CD3 bi-specific antibody MT110 (NCT00635596) and catumaxomab (Heiss et al , 2010; Goere et al , 2014; Bokemeyer et al , 2015), and ultimately to human engineered or fully human antibodies including ING-1 (Mosolits et al , 2004) and adecatumumab (MT201; Schmidt et al , 2012). Heiss et al (2010) found that catumaxomab provided a significant clinical benefit to GC patients with malignant ascites in a phase II/III trial.…”

“…Heiss et al (2010) found that catumaxomab provided a significant clinical benefit to GC patients with malignant ascites in a phase II/III trial. Another study has also demonstrated the safety and efficacy of catumaxomab in patients with resectable GC when serving as a part of a combined modality therapy (Bokemeyer et al , 2015). Moreover, a phase II trial of the intraperitoneal infusion of catumaxomab to treat postoperative GC patients with resectable primary lesions and peritoneal carcinomatosis is currently underway (Goere et al , 2014).…”