title: Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study.
abstract: 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.
authors: Second Department of Surgery Wakayama Medical University, Wakayama, Japan.
authors: Hiroki
authors: H
authors: Yamaue
authors: Second Department of Surgery Wakayama Medical University, Wakayama, Japan.
authors: Takuya
authors: T
authors: Tsunoda
authors: Second Department of Surgery Wakayama Medical University, Wakayama, Japan.
authors: Masaji
authors: M
authors: Tani
authors: Second Department of Surgery Wakayama Medical University, Wakayama, Japan.
authors: Motoki
authors: M
authors: Miyazawa
authors: Department of Gastroenterology Aichi Cancer Center Hospital, Aichi, Japan.
authors: Kenji
authors: K
authors: Yamao
authors: Department of Gastroenterology Aichi Cancer Center Hospital, Aichi, Japan.
authors: Nobumasa
authors: N
authors: Mizuno
authors: Hepatobiliary and Pancreatic Oncology Division National Cancer Center Hospital, Tokyo, Japan.
authors: Takuji
authors: T
authors: Okusaka
authors: Hepatobiliary and Pancreatic Oncology Division National Cancer Center Hospital, Tokyo, Japan.
authors: Hideki
authors: H
authors: Ueno
authors: Department of Gastroenterology Shizuoka Cancer Center, Shizuoka, Japan.
authors: Narikazu
authors: N
authors: Boku
authors: Department of Gastroenterology Shizuoka Cancer Center, Shizuoka, Japan.
authors: Akira
authors: A
authors: Fukutomi
authors: Hepatobiliary and Pancreatic Division Cancer Institute Hospital, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Ishii
authors: Hepatobiliary and Pancreatic Medical Oncology Division Kanagawa Cancer Center Hospital, Kanagawa, Japan.
authors: Shinichi
authors: S
authors: Ohkawa
authors: Department of Gastroenterology National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
authors: Masayuki
authors: M
authors: Furukawa
authors: Center for Gastroenterology Teine-Keijinkai Hospital, Hokkaido, Japan.
authors: Hiroyuki
authors: H
authors: Maguchi
authors: Division of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital East, Chiba, Japan.
authors: Masafumi
authors: M
authors: Ikeda
authors: Dept Genome Biology Kinki University School of Medicine, Osaka, Japan.
authors: Yosuke
authors: Y
authors: Togashi
authors: Dept Genome Biology Kinki University School of Medicine, Osaka, Japan.
authors: Kazuto
authors: K
authors: Nishio
authors: Department of Integrated Science and Engineering for Sustainable society Chuo University, Tokyo, Japan.
authors: Yasuo
authors: Y
authors: Ohashi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; C578462:arginyl-phenylalanyl-valyl-prolyl-aspartyl-glycyl-asparagyl-arginyl-isoleucine; D003841:Deoxycytidine; D040301:Vascular Endothelial Growth Factor Receptor-2; D000093542:Gemcitabine
keywords: Advanced pancreatic cancer; elpamotide; immunotherapy; peptide vaccine; phase II/III