PMID- 30500939
OWN - NLM
STAT- MEDLINE
DCOM- 20200504
LR  - 20200505
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 21
IP  - 3
DP  - 2019 Feb 19
TI  - A randomized, double-blind, phase III trial of personalized peptide vaccination 
      for recurrent glioblastoma.
PG  - 348-359
LID - 10.1093/neuonc/noy200 [doi]
AB  - BACKGROUND: We conducted a phase III trial of personalized peptide vaccination 
      (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a 
      new treatment modality. METHODS: We randomly assigned 88 recurrent glioblastoma 
      patients to receive PPV (n = 58) or the placebo (n = 30) at a 2-to-1 ratio. Four 
      of 12 warehouse peptides selected based on preexisting peptide-specific 
      immunoglobulin G levels or the corresponding placebos were injected 1x/week for 
      12 weeks. RESULTS: Our trial met neither the primary (overall survival [OS]) nor 
      secondary endpoints. Unfavorable factors for OS of 58 PPV patients compared with 
      30 placebo patients were SART2-93 peptide selection (n = 13 vs 8, hazard ratio 
      [HR]: 15.9), >/=70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), 
      and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the 
      median OS for PPV patients without SART2-93 selection plus one of these 3 
      favorable factors (<70 y old, </=70 kg, or PS0-2) was significantly longer than 
      that for the corresponding placebo patients (HR: 0.49, 0.44, and 0.51), 
      respectively. Preexisting immunity against both all 12 warehouse peptides besides 
      SART2-93 and the other cytotoxic T lymphocyte epitope peptides was significantly 
      depressed in the patients with SART2-93 selection (n = 21) compared with that of 
      the patients without SART2-93 selection (n = 67). Biomarkers correlative for 
      favorable OS of the PPV patients were a lower percentage of CD11b+CD14+HLA-DRlow 
      immunosuppressive monocytes and a higher percentage of CD4+CD45RA- activated T 
      cells, the intermediate levels of chemokine C-C ligand 2 (CCL2), vascular 
      endothelial growth factor, interleukin (IL)-6, IL-17, or haptoglobin, 
      respectively. CONCLUSION: This phase III trial met neither the primary nor 
      secondary endpoints.
CI  - (c) The Author(s) 2018. Published by Oxford University Press on behalf of the 
      Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Narita, Yoshitaka
AU  - Narita Y
AD  - National Cancer Center Hospital, Tokyo, Japan.
FAU - Arakawa, Yoshiki
AU  - Arakawa Y
AD  - Kyoto University Graduate School of Medicine, Kyoto, Japan.
FAU - Yamasaki, Fumiyuki
AU  - Yamasaki F
AD  - Hiroshima University Graduate School of Biomedical and Health Sciences, 
      Hiroshima, Japan.
FAU - Nishikawa, Ryo
AU  - Nishikawa R
AD  - Saitama Medical University International Medical Center, Saitama, Japan.
FAU - Aoki, Tomokazu
AU  - Aoki T
AD  - National Hospital Organization, Kyoto Medical Center, Kyoto, Japan.
FAU - Kanamori, Masayuki
AU  - Kanamori M
AD  - Tohoku University Graduate School of Medicine, Miyagi, Japan.
FAU - Nagane, Motoo
AU  - Nagane M
AD  - Kyorin University Faculty of Medicine, Tokyo, Japan.
FAU - Kumabe, Toshihiro
AU  - Kumabe T
AD  - Kitasato University School of Medicine, Kanagawa, Japan.
FAU - Hirose, Yuichi
AU  - Hirose Y
AD  - Fujita Health University School of Medicine, Aichi, Japan.
FAU - Ichikawa, Tomotsugu
AU  - Ichikawa T
AD  - Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical 
      Sciences, Okayama, Japan.
FAU - Kobayashi, Hiroyuki
AU  - Kobayashi H
AD  - Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
FAU - Fujimaki, Takamitsu
AU  - Fujimaki T
AD  - Saitama Medical University Hospital, Saitama, Japan.
FAU - Goto, Hisaharu
AU  - Goto H
AD  - Yamaguchi University School of Medicine, Yamaguchi, Japan.
FAU - Takeshima, Hideo
AU  - Takeshima H
AD  - Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
FAU - Ueba, Tetsuya
AU  - Ueba T
AD  - Kochi Medical School, Kochi, Japan.
FAU - Abe, Hiroshi
AU  - Abe H
AD  - Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
FAU - Tamiya, Takashi
AU  - Tamiya T
AD  - Kagawa University Faculty of Medicine, Kagawa, Japan.
FAU - Sonoda, Yukihiko
AU  - Sonoda Y
AD  - Yamagata University Faculty of Medicine, Yamagata, Japan.
FAU - Natsume, Atsushi
AU  - Natsume A
AD  - Nagoya University Graduate School of Medicine, Aichi, Japan.
FAU - Kakuma, Tatsuyuki
AU  - Kakuma T
AD  - Biostatistics Center, Kurume University, Fukuoka, Japan.
FAU - Sugita, Yasuo
AU  - Sugita Y
AD  - Kurume University School of Medicine, Fukuoka, Japan.
FAU - Komatsu, Nobukazu
AU  - Komatsu N
AD  - Kurume University School of Medicine, Fukuoka, Japan.
FAU - Yamada, Akira
AU  - Yamada A
AD  - Kurume University School of Medicine, Fukuoka, Japan.
FAU - Sasada, Tetsuro
AU  - Sasada T
AD  - Cancer Vaccine Center, Kanagawa Cancer Center Research Institute, Kanagawa, 
      Japan.
FAU - Matsueda, Satoko
AU  - Matsueda S
AD  - Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, USA.
FAU - Shichijo, Shigeki
AU  - Shichijo S
AD  - Cancer Vaccine Center, Kurume University, Fukuoka, Japan.
FAU - Itoh, Kyogo
AU  - Itoh K
AD  - Cancer Vaccine Center, Kurume University, Fukuoka, Japan.
FAU - Terasaki, Mizuhiko
AU  - Terasaki M
AD  - Kurume University School of Medicine, Fukuoka, Japan.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Vaccines, Subunit)
RN  - EC 5.1.3.19 (DSE protein, human)
SB  - IM
CIN - Neuro Oncol. 2019 Feb 19;21(3):289-290. PMID: 31222359
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Antigens, Neoplasm/*immunology
MH  - Brain Neoplasms/*drug therapy/immunology/metabolism
MH  - Cancer Vaccines/*therapeutic use
MH  - DNA-Binding Proteins/immunology
MH  - Female
MH  - Glioblastoma/*drug therapy/immunology/metabolism
MH  - HLA-A24 Antigen/metabolism
MH  - Humans
MH  - Karnofsky Performance Status
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/immunology
MH  - Neoplasm Recurrence, Local/*drug therapy/immunology/metabolism
MH  - Precision Medicine
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Survival Rate
MH  - Treatment Outcome
MH  - Vaccines, Subunit/*therapeutic use
MH  - Young Adult
PMC - PMC6380422
OTO - NOTNLM
OT  - biomarker for overall survival
OT  - personalized peptide vaccine
OT  - phase III trial
OT  - pre-existing immunity
OT  - recurrent glioblastoma
EDAT- 2018/12/01 06:00
MHDA- 2020/05/06 06:00
PMCR- 2020/02/19
CRDT- 2018/12/01 06:00
PHST- 2018/12/01 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2018/12/01 06:00 [entrez]
PHST- 2020/02/19 00:00 [pmc-release]
AID - 5219198 [pii]
AID - noy200 [pii]
AID - 10.1093/neuonc/noy200 [doi]
PST - ppublish
SO  - Neuro Oncol. 2019 Feb 19;21(3):348-359. doi: 10.1093/neuonc/noy200.