A randomized phase III trial of personalized peptide vaccination for castration‑resistant prostate cancer progressing after docetaxel

Noguchi,Masanori; Fujimoto,Kiyohide; Arai,Gaku; Uemura,Hiroji; Hashine,Katsuyoshi; Matsumoto,Hiroaki; Fukasawa,Satoshi; Kohjimoto,Yasuo; Nakatsu,Hideomi; Takenaka,Atsushi; Fujisawa,Masato; Uemura,Hirotsugu; Naito,Seiji; Egawa,Shin; Fujimoto,Hiroyuki; Hinotsu,Shiro; Itoh,Kyogo

doi:10.3892/or.2020.7847

A randomized phase III trial of personalized peptide vaccination for castration‑resistant prostate cancer progressing after docetaxel

Authors:
- Masanori Noguchi
- Kiyohide Fujimoto
- Gaku Arai
- Hiroji Uemura
- Katsuyoshi Hashine
- Hiroaki Matsumoto
- Satoshi Fukasawa
- Yasuo Kohjimoto
- Hideomi Nakatsu
- Atsushi Takenaka
- Masato Fujisawa
- Hirotsugu Uemura
- Seiji Naito
- Shin Egawa
- Hiroyuki Fujimoto
- Shiro Hinotsu
- Kyogo Itoh
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Affiliations: Cancer Vaccine Center and Department of Urology, Kurume University, Kurume, Fukuoka 839‑0863, Japan, Department of Urology, Nara Medical University Hospital, Kashihara, Nara 634‑8522, Japan, Department of Urology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama 343‑8555, Japan, Department of Urology, Yokohama City University Medical Center, Yokohama, Kanagawa 232‑0024, Japan, Department of Urology, Shikoku Cancer Center, Matsuyama, Ehime 791‑0280, Japan, Department of Urology, Yamaguchi University Hospital, Ube, Yamaguchi 755‑8505, Japan, Department of Urology, Chiba Cancer Center, Chiba, Chiba 260‑8717, Japan, Department of Urology, Wakayama Medical University Hospital, Wakayama, Wakayama 641‑8510, Japan, Department of Urology, Asahi General Hospital, Asahi, Chiba 289‑2511, Japan, Department of Urology, Tottori University Hospital, Yonago, Tottori 683‑8504, Japan, Department of Urology, Kobe University Hospital, Kobe, Hyogo 650‑0017, Japan, Department of Urology, Kindai University Hospital, Sayama, Osaka 589‑8511, Japan, Department of Urology, Sanshinkai Hara Hospital, Fukuoka, Fukuoka 812‑0033, Japan, Department of Urology, The Jikei University Hospital, Minatoku, Tokyo 105‑8471, Japan, Department of Urology, National Cancer Center Hospital, Chyuoku, Tokyo 104‑0045, Japan, Department of Urology, Sapporo Medical University, Sapporo, Hokkaido 060‑8543, Japan
Published online on: November 11, 2020 https://doi.org/10.3892/or.2020.7847
Pages: 159-168
Copyright: © Noguchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

First‑line chemotherapy for men with metastatic castration‑resistant prostate cancer (mCRPC) has been employed to improve overall survival (OS) and progression‑free survival (PFS). However, several new agents for CRPC after first‑line chemotherapy prolonged survival by only a few months. To develop a new treatment modality, we conducted a phase III randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)‑A24‑positive patients with castration‑resistant prostate cancer (CRPC) for whom docetaxel chemotherapy failed. This randomized, double‑blind, placebo‑controlled, phase III trial was carried out at 68 medical centers in Japan. Patients were randomly assigned at a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on pre‑existing peptide‑specific immunoglobulin G levels or the corresponding placebo were subcutaneously injected in 6 doses weekly and then bi‑weekly following the maximum of 30 doses until disease progression. The primary end‑point was overall survival (OS). Efficacy analyses were performed by the full analysis set. Between August 2013 and April 2016, 310 patients were randomly assigned, and 306 patients were analyzed. Baseline characteristics were balanced between groups. The estimated median OS was 16.1 months [95% confidence interval (CI), 13‑18.2] with PPV and 16.9 months (95% CI, 13.1‑20.4) with placebo [hazard ratio (HR), 1.04, 95% CI, 0.80‑1.37; P=0.77]. Grade ≥3 adverse events were observed in 41% of both groups. The analysis of treatment arm effects among subgroups revealed lower HRs for OS in favor of the PPV arm in patients with <64% neutrophils (HR, 0.55, 95% CI, 0.33‑0.93; P=0.03) or ≥26% lymphocytes (HR, 0.70, 95% CI, 0.52‑0.92; P=0.02) at baseline. PPV did not prolong OS in HLA‑A24‑positive patients with CRPC progressing after docetaxel chemotherapy. Subgroup analysis suggested that the patients with a lower proportion of neutrophils or a higher proportion of lymphocytes at baseline can receive survival benefits from PPV treatment.

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