An open-label, randomized phase II trial of personalized peptide vaccination in patients with bladder cancer that progressed after platinum-based chemotherapy

Masanori Noguchi, Kazumasa Matsumoto, Hirotsugu Uemura, Gaku Arai, Masatoshi Eto, Seiji Naito, Chikara Ohyama, Yasutomo Nasu, Masatoshi Tanaka, Fukuko Moriya, Shigetaka Suekane, Satoko Matsueda, Nobukazu Komatsu, Tetsuro Sasada, Akira Yamada, Tatsuyuki Kakuma, Kyogo Itoh

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Purpose: The prognosis of platinum-based chemotherapy-resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity. Experimental Design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity. Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4-1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34-0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5-12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8-6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions. Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results.

Original languageEnglish
Pages (from-to)54-60
Number of pages7
JournalClinical Cancer Research
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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Platinum
Urinary Bladder Neoplasms
Vaccination
Drug Therapy
Peptides
Confidence Intervals
Disease-Free Survival
Survival
Injections
Cancer Vaccines
HLA Antigens
Drug-Related Side Effects and Adverse Reactions
Immunity
Research Design
Immunoglobulin G

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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An open-label, randomized phase II trial of personalized peptide vaccination in patients with bladder cancer that progressed after platinum-based chemotherapy. / Noguchi, Masanori; Matsumoto, Kazumasa; Uemura, Hirotsugu; Arai, Gaku; Eto, Masatoshi; Naito, Seiji; Ohyama, Chikara; Nasu, Yasutomo; Tanaka, Masatoshi; Moriya, Fukuko; Suekane, Shigetaka; Matsueda, Satoko; Komatsu, Nobukazu; Sasada, Tetsuro; Yamada, Akira; Kakuma, Tatsuyuki; Itoh, Kyogo.

In: Clinical Cancer Research, Vol. 22, No. 1, 01.01.2016, p. 54-60.

Research output: Contribution to journalArticle

Noguchi, M, Matsumoto, K, Uemura, H, Arai, G, Eto, M, Naito, S, Ohyama, C, Nasu, Y, Tanaka, M, Moriya, F, Suekane, S, Matsueda, S, Komatsu, N, Sasada, T, Yamada, A, Kakuma, T & Itoh, K 2016, 'An open-label, randomized phase II trial of personalized peptide vaccination in patients with bladder cancer that progressed after platinum-based chemotherapy', Clinical Cancer Research, vol. 22, no. 1, pp. 54-60. https://doi.org/10.1158/1078-0432.CCR-15-1265
Noguchi, Masanori ; Matsumoto, Kazumasa ; Uemura, Hirotsugu ; Arai, Gaku ; Eto, Masatoshi ; Naito, Seiji ; Ohyama, Chikara ; Nasu, Yasutomo ; Tanaka, Masatoshi ; Moriya, Fukuko ; Suekane, Shigetaka ; Matsueda, Satoko ; Komatsu, Nobukazu ; Sasada, Tetsuro ; Yamada, Akira ; Kakuma, Tatsuyuki ; Itoh, Kyogo. / An open-label, randomized phase II trial of personalized peptide vaccination in patients with bladder cancer that progressed after platinum-based chemotherapy. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 1. pp. 54-60.
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abstract = "Purpose: The prognosis of platinum-based chemotherapy-resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity. Experimental Design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity. Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95{\%} confidence interval (CI), 0.4-1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95{\%} CI, 0.34-0.99, P = 0.049), with median OS of 7.9 months (95{\%} CI, 3.5-12.0) in the PPV plus BSC and 4.1 months (95{\%} CI, 2.8-6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions. Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results.",
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T1 - An open-label, randomized phase II trial of personalized peptide vaccination in patients with bladder cancer that progressed after platinum-based chemotherapy

AU - Noguchi, Masanori

AU - Matsumoto, Kazumasa

AU - Uemura, Hirotsugu

AU - Arai, Gaku

AU - Eto, Masatoshi

AU - Naito, Seiji

AU - Ohyama, Chikara

AU - Nasu, Yasutomo

AU - Tanaka, Masatoshi

AU - Moriya, Fukuko

AU - Suekane, Shigetaka

AU - Matsueda, Satoko

AU - Komatsu, Nobukazu

AU - Sasada, Tetsuro

AU - Yamada, Akira

AU - Kakuma, Tatsuyuki

AU - Itoh, Kyogo

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Purpose: The prognosis of platinum-based chemotherapy-resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity. Experimental Design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity. Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4-1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34-0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5-12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8-6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions. Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results.

AB - Purpose: The prognosis of platinum-based chemotherapy-resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity. Experimental Design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity. Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4-1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34-0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5-12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8-6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions. Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results.

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