Kazuhiro Yoshimura1, Takafumi Minami1, Masahiro Nozawa1, Takahiro Kimura2, Shin Egawa2, Hiroyuki Fujimoto3, Akira Yamada4, Kyogo Itoh5, Hirotsugu Uemura6. 1. Department of Urology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. 2. Department of Urology, Jikei University School of Medicine, Minato-ku, Tokyo, Japan. 3. Department of Urology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan. 4. Kurume University Research Center for Innovative Cancer Therapy, Kurume, Fukuoka, Japan. 5. Kurume University Cancer Vaccine Center, Kurume, Fukuoka, Japan. 6. Department of Urology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. Electronic address: huemura@med.kindai.ac.jp.
Abstract
BACKGROUND: It is well known that the prognosis of castration-resistant prostate cancer (CRPC) is poor, and several immunotherapeutic strategies have been applied to the clinical trials. Research on immunotherapy has been of special interest for the treatment of CRPC for years. OBJECTIVE: To evaluate the safety of personalized peptide vaccine (PPV) immunotherapy and its clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: A phase 2 randomized controlled trial of PPV immunotherapy with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive CRPC began in 2008. Eligible patients (prostate-specific antigen [PSA] <10 ng/ml) were human leukocyte antigen (HLA) A02, A24, or A03 superfamily positive and had asymptomatic or minimally symptomatic CRPC. Patients were allocated (1:1) to PPV plus dexamethasone (1mg/d) or to dexamethasone (1mg/d) alone. A maximum of four HLA-matched peptides (each 3mg) was selected based on the preexisting immunoglobulin G responses against the 24 warehouse peptides and administered every 2 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA, progression-free survival (PFS), time to initiation of chemotherapy, and overall survival (OS) were analyzed using the Kaplan-Meier method, a log-rank test, and proportional hazard analysis. RESULTS AND LIMITATIONS: Overall, 37 patients receivedpeptide vaccinations and 35 received dexamethasone alone. The primary end point was PSA PFS, which was significantly longer in the vaccination group than in the dexamethasone group (22.0 vs 7.0 mo; p=0.0076). Median OS was also significantly longer in the vaccination group (73.9 vs 34.9 mo; p=0.00084). The relatively small number of patients enrolled is the major limitation of the study. CONCLUSIONS:PPV immunotherapy was well tolerated and associated with longer PSA PFS and OS in men with chemotherapy-naive CRPC. A larger phase 3 study is needed to confirm our findings. PATIENT SUMMARY: We compared clinical outcomes of the treatment with personalized peptide vaccine plus dexamethasone versus dexamethasone alone. Our data provide promising evidence of clinical benefit for peptide vaccines. TRIAL REGISTRATION: UMIN-CTR: 000000959.
RCT Entities:
BACKGROUND: It is well known that the prognosis of castration-resistant prostate cancer (CRPC) is poor, and several immunotherapeutic strategies have been applied to the clinical trials. Research on immunotherapy has been of special interest for the treatment of CRPC for years. OBJECTIVE: To evaluate the safety of personalized peptide vaccine (PPV) immunotherapy and its clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: A phase 2 randomized controlled trial of PPV immunotherapy with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive CRPC began in 2008. Eligible patients (prostate-specific antigen [PSA] <10 ng/ml) were human leukocyte antigen (HLA) A02, A24, or A03 superfamily positive and had asymptomatic or minimally symptomatic CRPC. Patients were allocated (1:1) to PPV plus dexamethasone (1mg/d) or to dexamethasone (1mg/d) alone. A maximum of four HLA-matched peptides (each 3mg) was selected based on the preexisting immunoglobulin G responses against the 24 warehouse peptides and administered every 2 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA, progression-free survival (PFS), time to initiation of chemotherapy, and overall survival (OS) were analyzed using the Kaplan-Meier method, a log-rank test, and proportional hazard analysis. RESULTS AND LIMITATIONS: Overall, 37 patients received peptide vaccinations and 35 received dexamethasone alone. The primary end point was PSA PFS, which was significantly longer in the vaccination group than in the dexamethasone group (22.0 vs 7.0 mo; p=0.0076). Median OS was also significantly longer in the vaccination group (73.9 vs 34.9 mo; p=0.00084). The relatively small number of patients enrolled is the major limitation of the study. CONCLUSIONS: PPV immunotherapy was well tolerated and associated with longer PSA PFS and OS in men with chemotherapy-naive CRPC. A larger phase 3 study is needed to confirm our findings. PATIENT SUMMARY: We compared clinical outcomes of the treatment with personalized peptide vaccine plus dexamethasone versus dexamethasone alone. Our data provide promising evidence of clinical benefit for peptide vaccines. TRIAL REGISTRATION: UMIN-CTR: 000000959.
Authors: Annika Nelde; Yacine Maringer; Tatjana Bilich; Helmut R Salih; Malte Roerden; Jonas S Heitmann; Ana Marcu; Jens Bauer; Marian C Neidert; Claudio Denzlinger; Gerald Illerhaus; Walter Erich Aulitzky; Hans-Georg Rammensee; Juliane S Walz Journal: Front Immunol Date: 2021-07-08 Impact factor: 7.561
Authors: Andrea Garofalo; Lynette Sholl; Brendan Reardon; Amaro Taylor-Weiner; Ali Amin-Mansour; Diana Miao; David Liu; Nelly Oliver; Laura MacConaill; Matthew Ducar; Vanesa Rojas-Rudilla; Marios Giannakis; Arezou Ghazani; Stacy Gray; Pasi Janne; Judy Garber; Steve Joffe; Neal Lindeman; Nikhil Wagle; Levi A Garraway; Eliezer M Van Allen Journal: Genome Med Date: 2016-07-26 Impact factor: 11.117