Combination gemcitabine and WT1 peptide vaccination improves progression-free survival in advanced pancreatic ductal adenocarcinoma: A phase II randomized study

Sumiyuki Nishida, Takeshi Ishikawa, Shinichi Egawa, Shigeo Koido, Hiroaki Yanagimoto, Jun Ishii, Yoshihide Kanno, Satoshi Kokura, Hiroaki Yasuda, Mari Saito Oba, Maho Sato, Soyoko Morimoto, Fumihiro Fujiki, Hidetoshi Eguchi, Hiroaki Nagano, Atsushi Kumanogoh, Michiaki Unno, Masanori Kon, Hideaki Shimada, Kei ItoSadamu Homma, Yoshihiro Oka, Satoshi Morita, Haruo Sugiyama

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Abstract

We investigated the efficacy of a Wilms' tumor gene 1 (WT1) vaccine combined with gemcitabine (GEMWT1) and compared it with gemcitabine (GEM) monotherapy for advanced pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II study. We randomly assigned HLA-A02:01– or HLA-A24:02–positive patients with advanced PDAC to receive GEMWT1 or GEM. We assessed WT1-specific immune responses via delayed-type hypersensitivity (DTH) to the WT1 peptide and a tetramer assay to detect WT1-specific cytotoxic T lymphocytes (WT1-CTL). Of 91 patients enrolled, 85 were evaluable (GEMWT1: n = 42; GEM: n = 43). GEMWT1 prolonged progression-free survival [PFS; hazard ratio (HR), 0.66; P = 0.084] and improved overall survival rate at 1 year (1-year OS%; GEMWT1: 35.7%; GEM: 20.9%). However, the difference in OS was not significant (HR: 0.82; P = 0.363). These effects were particularly evident in metastatic PDAC (PFS: HR 0.51, P = 0.0017; 1-year OS%: GEMWT1 27.3%; GEM 11.8%). The combination was well tolerated, with no unexpected serious adverse events. In patients with metastatic PDAC, PFS in the DTH-positive GEMWT1 group was significantly prolonged, with a better HR of 0.27 compared with the GEM group, whereas PFS in the DTH-negative GEMWT1 group was similar to that in the GEM group (HR 0.86; P = 0.001). DTH positivity was associated with an increase in WT1-CTLs induced by the WT1 vaccine. GEM plus the WT1 vaccine prolonged PFS and may improve 1-year OS% in advanced PDAC. These clinical effects were associated with the induction of WT1-specific immune responses.

Original languageEnglish
Pages (from-to)320-331
Number of pages12
JournalCancer Immunology Research
Volume6
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cancer Research

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    Nishida, S., Ishikawa, T., Egawa, S., Koido, S., Yanagimoto, H., Ishii, J., Kanno, Y., Kokura, S., Yasuda, H., Oba, M. S., Sato, M., Morimoto, S., Fujiki, F., Eguchi, H., Nagano, H., Kumanogoh, A., Unno, M., Kon, M., Shimada, H., ... Sugiyama, H. (2018). Combination gemcitabine and WT1 peptide vaccination improves progression-free survival in advanced pancreatic ductal adenocarcinoma: A phase II randomized study. Cancer Immunology Research, 6(3), 320-331. https://doi.org/10.1158/2326-6066.CIR-17-0386