Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer; PEGASUS-PC Study.

Cancer science

PubMedID: 25867139

Yamaue H, Tsunoda T, Tani M, Miyazawa M, Yamao K, Mizuno N, Okusaka T, Ueno H, Boku N, Fukutomi A, Ishii H, Ohkawa S, Furukawa M, Maguchi H, Ikeda M, Togashi Y, Nishio K, Ohashi Y. Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer; PEGASUS-PC Study. Cancer Sci. 2015;.
Gemcitabine is a key drug for pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular Endothelial Growth Factor-receptor 2 (VEGFR2) is an essential target for tumor angiogenesis, and we have executed a phase I clinical trial using gemcitabine and VEGFR2-peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been conducted for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. PATIENTS
were assigned to either Active group (elpamotide+gemcitabine) or Placebo group (placebo+gemcitabine) in 2:1 ratio by the dynamic allocation method.Patients were assigned to either Active group (elpamotide+gemcitabine) or Placebo group (placebo+gemcitabine) in 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test (H-F) was applied to the statistical analysis in this study to evaluate the time-lagged effect of immunotherapy appropriately. A total of 153 patients (A=100, P=53) were included in the analysis. No statistically significant differences were found between the 2 groups in the prolongation of overall survival [H-F p value; 0. 918, log-rank p value; 0. 897, Hazard Ratio; 0. 87, 95% confidence interval (CI), 0. 486-1. 557]. Median survival time was 8. 36 months (95% CI, 7. 46-10. 18) for Active group and 8. 54 months (95% CI, 7. 33-10. 84) for Placebo group. The toxicity observed in both groups was manageable. Combination therapy of elpamotide with gemcitabine was well tolerated. Despite the lack of benefit in overall survival, subgroup analysis suggested that the patients, who experienced severe injection site reaction (ISR), such as ulceration and erosion, might have better survival. The clinical registration number is UMIN000001664. This article is protected by copyright. All rights reserved.