Randomized phase II/III clinical trial of elpamotide for patients with advanced
pancreatic cancer: PEGASUS-PC Study.
Author(s): Yamaue H(1), Tsunoda T(1), Tani M(1), Miyazawa M(1), Yamao K(2), Mizuno N(2),
Okusaka T(3), Ueno H(3), Boku N(4), Fukutomi A(4), Ishii H(5), Ohkawa S(6),
Furukawa M(7), Maguchi H(8), Ikeda M(9), Togashi Y(10), Nishio K(10), Ohashi
Y(11).
Affiliation(s): Author information:
(1)Second Department of Surgery Wakayama Medical University, Wakayama, Japan.
(2)Department of Gastroenterology Aichi Cancer Center Hospital, Aichi, Japan.
(3)Hepatobiliary and Pancreatic Oncology Division National Cancer Center
Hospital, Tokyo, Japan. (4)Department of Gastroenterology Shizuoka Cancer Center,
Shizuoka, Japan. (5)Hepatobiliary and Pancreatic Division Cancer Institute
Hospital, Tokyo, Japan. (6)Hepatobiliary and Pancreatic Medical Oncology Division
Kanagawa Cancer Center Hospital, Kanagawa, Japan. (7)Department of
Gastroenterology National Hospital Organization Kyushu Cancer Center, Fukuoka,
Japan. (8)Center for Gastroenterology Teine-Keijinkai Hospital, Hokkaido, Japan.
(9)Division of Hepatobiliary and Pancreatic Oncology National Cancer Center
Hospital East, Chiba, Japan. (10)Dept Genome Biology Kinki University School of
Medicine, Osaka, Japan. (11)Department of Integrated Science and Engineering for
Sustainable society Chuo University, Tokyo, Japan.
Publication date & source: 2015, Cancer Sci. , 106(7):883-90
Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with
its limitation in clinical benefits, the development of another potent
therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an
essential target for tumor angiogenesis, and we have conducted a phase I clinical
trial using gemcitabine and vascular endothelial growth factor receptor 2 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 carried out for pancreatic cancer. The eligibility criteria
included locally advanced or metastatic pancreatic cancer. Patients were assigned
to either the Active group (elpamotide + gemcitabine) or Placebo group
(placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The
primary endpoint was overall survival. The Harrington-Fleming test was applied to
the statistical analysis in this study to evaluate the time-lagged effect of
immunotherapy appropriately. A total of 153 patients (Active group, n = 100;
Placebo group, n = 53) were included in the analysis. No statistically
significant differences were found between the two groups in the prolongation of
overall survival (Harrington-Fleming 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 the Active group and 8.54 months
(95% CI, 7.33-10.84) for the 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, such
as ulceration and erosion, might have better survival.
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