Z Gastroenterol 2011; 49 - P016
DOI: 10.1055/s-0031-1285288

An open-label, multicenter biomarker-oriented phase II trial of sunitinib for patients with chemo-refractory advanced gastric cancer

M Moehler 1, A Mueller 1, JT Hartmann 2, MP Ebert 3, SE Al-Batran 4, P Reimer 5, M Weihrauch 6, F Lordick 7, T Trarbach 8, S Biesterfeld 9, M Kabisch 10, D Wachtlin 10 PR Galle 1, Arbeitsgemeinschaft Internistische Onkologie
  • 1University Mainz, I. Dept. Medicine, Mainz, Germany
  • 2University Clinic of Kiel, Kiel, Germany
  • 3University Hospital, Technical University Munich, Medical Department II, Munich, Germany
  • 4Clinic Northwest, Department of Oncology and Hematology, Frankfurt, Germany
  • 5University of Wuerzburg, 2nd Department of Internal Medicine, Wuerzburg, Germany
  • 6University of Köln, Molecular Tumour Biology and Tumour Immunology, Köln, Germany
  • 7City Clinic Braunschweig, 3rd Medical Department, Braunschweig, Germany
  • 8University Hospital of Essen, Department of Medicine, Essen, Germany
  • 9Uniklinik Mainz, Department of Pathology, Mainz, Germany
  • 10University Mainz, Interdisciplinary Center of Clinical Studies, Mainz, Germany

Background: Tumour angiogenesis, growth, and metastasis can be inhibited by blocking receptor tyrosine kinases (RTKs) overexpressed in human advanced gastric cancer (AGC), including vascular endothelial growth factor receptors (VEGFRs), epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptors (PDGFRs). Sunitinib malate, an oral, multi-targeted tyrosine kinase inhibitor of VEGFR1, -2, and -3, PDGFR-α and -β, and several other related RTKs was investigated Sunitinib in pretreated patients with AGC. Preplanned analyses of tumour biomarkers on treatment outcome were performed.

Patients and methods: Patients received sunitinib 50mg/day for 4 weeks with 2 weeks rest until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety.

Results: Fifty two patients were enrolled and treated (safety population, SP). In the intention to treat population (n=51); the ORR was 3.9%, median PFS was 1.28 months [95% CI, 1.18–1.90], median OS was 5.81 months [95% CI, 3.48–12.32], the estimated one-year survival rate was 23.7% [95%CI: 12.8–36.5]. In subgroup analyses, tumour VEGF-C expression compared with no expression was associated with significantly shorter median PFS (1.23 vs. 2.86 months, logrank p=0.0119) but there was no difference in tumour control rate (p=0.142). In the SP, serious adverse events occurred in 26 patients, leading to 13 deaths, all sunitinib unrelated. Thirty eight patients died from progressive disease, nine died <60 days after treatment start.

Conclusion: The preliminary activity and manageable toxicity observed suggests that sunitinib has defined clinical value as second-line treatment for AGC. Following our additional positive in vitro data we are currently conducting a randomized phase II study of second-line FOLFIRI +/- sunitinib (NCT01020630, clinical trials.gov) in the treatment of AGC.