title: Phase II trial of combination therapy of gemcitabine plus anti-angiogenic vaccination of elpamotide in patients with advanced or recurrent biliary tract cancer.
abstract: Background Elpamotide is an HLA-A*24:02-restricted epitope peptide of vascular endothelial growth factor receptor 2 (VEGFR-2) and induces cytotoxic T lymphocytes (CTLs) against VEGFR-2/KDR. Given the high expression of VEGFR-2 in biliary tract cancer, combination chemoimmunotherapy with elpamotide and gemcitabine holds promise as a new therapy. Patients and Methods Patients with unresectable advanced or recurrent biliary tract cancer were included in this single-arm phase II trial, with the primary endpoint of overall survival. Survival analysis was performed in comparison with historical control data. The patients concurrently received gemcitabine once a week for 3 weeks (the fourth week was skipped) and elpamotide once a week for 4 weeks. Results Fifty-five patients were registered, of which 54 received the regimen and were included in the full analysis set as well as the safety analysis set. Median survival was 10.1 months, which was longer than the historical control, and the 1-year survival rate was 44.4%. Of these patients, injection site reactions were observed in 64.8%, in whom median survival was significantly longer (14.8 months) compared to those with no injection site reactions (5.7 months). The response rate was 18.5%, and all who responded exhibited injection site reactions. Serious adverse reactions were observed in five patients (9%), and there were no treatment-related deaths. Conclusion Gemcitabine and elpamotide combination therapy was tolerable and had a moderate antitumor effect. For future development of therapies, it will be necessary to optimize the target population for which therapeutic effects could be expected.
authors.affiliation: Gastroenterological Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan, mahsanmahsan2000@yahoo.co.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Matsuyama
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: J
authors.initials: J
authors.lastname: Furuse
authors.forename: S
authors.initials: S
authors.lastname: Ohkawa
authors.forename: H
authors.initials: H
authors.lastname: Maguchi
authors.forename: N
authors.initials: N
authors.lastname: Mizuno
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Ioka
authors.forename: T
authors.initials: T
authors.lastname: Ajiki
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Hakamada
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Yamaue
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
authors.forename: W
authors.initials: W
authors.lastname: Ichikawa
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000009:adverse effects / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C578462:arginyl-phenylalanyl-valyl-prolyl-aspartyl-glycyl-asparagyl-arginyl-isoleucine; D003841:Deoxycytidine; D040301:Vascular Endothelial Growth Factor Receptor-2; D000093542:Gemcitabine