PMID- 33200227 OWN - NLM STAT- MEDLINE DCOM- 20210830 LR - 20210830 IS - 1791-2431 (Electronic) IS - 1021-335X (Print) IS - 1021-335X (Linking) VI - 45 IP - 1 DP - 2021 Jan TI - A randomized phase III trial of personalized peptide vaccination for castration‑resistant prostate cancer progressing after docetaxel. PG - 159-168 LID - 10.3892/or.2020.7847 [doi] AB - 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. FAU - Noguchi, Masanori AU - Noguchi M AD - Cancer Vaccine Center and Department of Urology, Kurume University, Kurume, Fukuoka 839‑0863, Japan. FAU - Fujimoto, Kiyohide AU - Fujimoto K AD - Department of Urology, Nara Medical University Hospital, Kashihara, Nara 634‑8522, Japan. FAU - Arai, Gaku AU - Arai G AD - Department of Urology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama 343‑8555, Japan. FAU - Uemura, Hiroji AU - Uemura H AD - Department of Urology, Yokohama City University Medical Center, Yokohama, Kanagawa 232‑0024, Japan. FAU - Hashine, Katsuyoshi AU - Hashine K AD - Department of Urology, Shikoku Cancer Center, Matsuyama, Ehime 791‑0280, Japan. FAU - Matsumoto, Hiroaki AU - Matsumoto H AD - Department of Urology, Yamaguchi University Hospital, Ube, Yamaguchi 755‑8505, Japan. FAU - Fukasawa, Satoshi AU - Fukasawa S AD - Department of Urology, Chiba Cancer Center, Chiba, Chiba 260‑8717, Japan. FAU - Kohjimoto, Yasuo AU - Kohjimoto Y AD - Department of Urology, Wakayama Medical University Hospital, Wakayama, Wakayama 641‑8510, Japan. FAU - Nakatsu, Hideomi AU - Nakatsu H AD - Department of Urology, Asahi General Hospital, Asahi, Chiba 289‑2511, Japan. FAU - Takenaka, Atsushi AU - Takenaka A AD - Department of Urology, Tottori University Hospital, Yonago, Tottori 683‑8504, Japan. FAU - Fujisawa, Masato AU - Fujisawa M AD - Department of Urology, Kobe University Hospital, Kobe, Hyogo 650‑0017, Japan. FAU - Uemura, Hirotsugu AU - Uemura H AD - Department of Urology, Kindai University Hospital, Sayama, Osaka 589‑8511, Japan. FAU - Naito, Seiji AU - Naito S AD - Department of Urology, Sanshinkai Hara Hospital, Fukuoka, Fukuoka 812‑0033, Japan. FAU - Egawa, Shin AU - Egawa S AD - Department of Urology, The Jikei University Hospital, Minatoku, Tokyo 105‑8471, Japan. FAU - Fujimoto, Hiroyuki AU - Fujimoto H AD - Department of Urology, National Cancer Center Hospital, Chyuoku, Tokyo 104‑0045, Japan. FAU - Hinotsu, Shiro AU - Hinotsu S AD - Department of Urology, Sapporo Medical University, Sapporo, Hokkaido 060‑8543, Japan. FAU - Itoh, Kyogo AU - Itoh K AD - Cancer Vaccine Center and Department of Urology, Kurume University, Kurume, Fukuoka 839‑0863, Japan. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial DEP - 20201111 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Cancer Vaccines) RN - 0 (HLA-A24 Antigen) RN - 0 (Vaccines, Subunit) RN - 15H5577CQD (Docetaxel) SB - IM MH - Aged MH - Aged, 80 and over MH - Cancer Vaccines/*therapeutic use MH - Docetaxel/*therapeutic use MH - Double-Blind Method MH - HLA-A24 Antigen/*analysis MH - Humans MH - Male MH - Middle Aged MH - Prostatic Neoplasms, Castration-Resistant/mortality/*therapy MH - *Vaccination MH - Vaccines, Subunit/therapeutic use PMC - PMC7709822 OTO - NOTNLM OT - prostate cancer OT - cancer vaccine OT - multiple‑peptide vaccine OT - immunotherapy OT - docetaxel EDAT- 2020/11/18 06:00 MHDA- 2021/08/31 06:00 PMCR- 2020/11/11 CRDT- 2020/11/17 06:24 PHST- 2020/06/06 00:00 [received] PHST- 2020/10/13 00:00 [accepted] PHST- 2020/11/18 06:00 [pubmed] PHST- 2021/08/31 06:00 [medline] PHST- 2020/11/17 06:24 [entrez] PHST- 2020/11/11 00:00 [pmc-release] AID - or-45-01-0159 [pii] AID - 10.3892/or.2020.7847 [doi] PST - ppublish SO - Oncol Rep. 2021 Jan;45(1):159-168. doi: 10.3892/or.2020.7847. Epub 2020 Nov 11.