Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA-A24-positive pancreatic adenocarcinoma.

Abstract

The prognosis of advanced pancreatic adenocarcinoma is still extremely poor. This study sought to determine the efficacy of, and immunological response to, peptide vaccination therapy in patients with this disease. In this multicenter randomized phase II study, patients with advanced pancreatic adenocarcinoma after gemcitabine and/or tegafur/gimeracil/oteracil were randomly assigned to 3 groups that each received a 2-step treatment course. In Step 1, the groups received treatments of: (i) survivin 2B peptide (SVN-2B) plus interferon-β (IFNβ); (ii) SVN-2B only; or (iii) placebo until the patients show progression. In Step 2, all patients who consented to participate received 4 treatments with SVN-2B plus IFNβ. The primary endpoint was progression-free survival (PFS) after initiation of Step 1 treatment. Secondary endpoints included immunological effects assessed by analysis of PBMCs after Step 1. Eighty-three patients were randomly assigned to receive SVN-2B plus IFNβ (n = 30), SVN-2B (n = 34), or placebo (n = 19). No significant improvement in PFS was observed. Survivin 2B-specific CTLs were found to be increased in the SVN-2B plus IFNβ group by tetramer assay. Among patients who participated in Step 2, those who had received SVN-2B plus IFNβ in Step 1 showed better overall survival compared with those who had received placebo in Step 1. Patients vaccinated with SVN-2B plus IFNβ did not have improved PFS, but showed significant immunological reaction after vaccination. Subgroup analysis suggested that a longer SVN-2B plus IFNβ vaccination protocol might confer survival benefit. (Clinical trial registration number: UMIN 000012146).

• Authors: Hiroaki Shima, Giichiro Tsurita, Satoshi Wada, Yoshihiko Hirohashi, Hiroshi Yasui, Hiroshi Hayashi, Takashi Miyakoshi, Kazue Watanabe, Aiko Murai, Hiroko Asanuma, Serina Tokita, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Yutaka Nakae, Osamu Sugita, Yoichi M Ito, Yasunori Ota, Yasutoshi Kimura, Goro Kutomi, Koichi Hirata, Toru Mizuguchi, Kohzoh Imai, Ichiro Takemasa, Noriyuki Sato, Toshihiko Torigoe
• Journal: Cancer science (Cancer Sci) Vol. 110 Issue 8 Pg. 2378-2385 (Aug 2019) ISSN: 1349-7006 [Electronic] England
• PMID: 31218770 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Cancer Vaccines
• Peptides
• Survivin
• Vaccines, Subunit
• Deoxycytidine
• Interferon-beta
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy)
• Adult
• Aged
• Aged, 80 and over
• Cancer Vaccines (therapeutic use)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Interferon-beta (therapeutic use)
• Male
• Middle Aged
• Pancreatic Neoplasms (drug therapy)
• Peptides (therapeutic use)
• Prognosis
• Progression-Free Survival
• Survivin (therapeutic use)
• Vaccination (methods)
• Vaccines, Subunit (therapeutic use)
• Gemcitabine