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. Clin Cancer Res; 1-7. ©2015 AACR.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2015 Nov 18 [Epub ahead of print]
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
Divisions of Clinical Research, Kurume University School of Medicine, Kurume, Japan. Department of Urology, Kurume University School of Medicine, Kurume, Japan. Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan. , Department of Urology, Kinki University Faculty of Medicine, Osaka, Japan. , Department of Urology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan. , Department of Urology, Kumamoto University, Kumamoto, Japan. , Department of Urology, Graduate School of Medical Sciences, University of Kyushu, Fukuoka, Japan. , Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. , Department of Urology, Okayama University Graduate School of Medicine, Okayama, Japan. , Department of Urology, Fukuoka University, Fukuoka, Japan. , Department of Pathology, Kurume University School of Medicine, Kurume, Japan. , Department of Urology, Kurume University School of Medicine, Kurume, Japan. , Cancer Vaccine Center, Kurume University School of Medicine, Kurume, Japan. , Kurume University School of Medicine, Kurume, Japan. , Department of Immunology, Kurume University School of Medicine, Kurume, Japan. , Cancer Vaccines, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan. , Bio-Statistics Center, Kurume University School of Medicine, Kurume, Japan. , Cancer Vaccine Center, Kurume University School of Medicine, Kurume, Japan.