An Open-Label, Randomized Phase II Trial of Personalized Peptide Vaccination in Patients with Bladder Cancer that Progressed after Platinum-Based Chemotherapy

作者：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

来源：Clinical Cancer Research, 2016, 22(1): 54-60.

DOI：10.1158/1078-0432.CCR-15-1265

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 end-points 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.

• 出版日期2016-1-1