Mixed 20-peptide cancer vaccine in combination with docetaxel and dexamethasone for castration-resistant prostate cancer: a randomized phase II trial.

Abstract

A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-naïve patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined with docetaxel and dexamethasone (n = 25) or placebo with docetaxel and dexamethasone (n = 26). The primary endpoint was the difference in prostate-specific antigen (PSA) decline between each treatment. The rates of > 50% PSA decline in the two arms were similar (56.5% versus 53.8%; P = 0.851). Human leukocyte antigen (HLA)-matched peptide-specific immunoglobulin G (P = 0.018) and CTL (P = 0.007) responses in the KRM-20 arm significantly increased after treatment. The addition of KRM-20 did not increase toxicity. There were no between-group differences in progression-free or overall survival (OS). The addition of KRM-20 was safe, and similar PSA decline and HLA-matched peptide-specific CTL and IgG responses increased in combination with docetaxel and dexamethasone in CRPC patients. Subgroup analysis suggested that this treatment is favorable for CRPC patients with ≥ 26% lymphocytes or PSA levels of < 11.2 ng/ml, but further clinical trials comparing OS are required.

• Authors: Masanori Noguchi, Gaku Arai, Shin Egawa, Chikara Ohyama, Seiji Naito, Kazumasa Matsumoto, Hirotsugu Uemura, Masayuki Nakagawa, Yasutomo Nasu, Masatoshi Eto, Shigetaka Suekane, Tetsuro Sasada, Shigeki Shichijo, Akira Yamada, Tatsuyuki Kakuma, Kyogo Itoh
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 69 Issue 5 Pg. 847-857 (May 2020) ISSN: 1432-0851 [Electronic] Germany
• PMID: 32025848 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Cancer Vaccines
• Vaccines, Subunit
• Docetaxel
• Dexamethasone
• KLK3 protein, human
• Kallikreins
• Prostate-Specific Antigen

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Cancer Vaccines (administration & dosage, adverse effects, immunology)
• Combined Modality Therapy (adverse effects, methods)
• Dexamethasone (administration & dosage, adverse effects)
• Docetaxel (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Administration Schedule
• Humans
• Infusions, Intravenous
• Injections, Subcutaneous
• Kallikreins (blood)
• Male
• Middle Aged
• Progression-Free Survival
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms, Castration-Resistant (blood, immunology, mortality, therapy)
• Response Evaluation Criteria in Solid Tumors
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccines, Subunit (administration & dosage, adverse effects, immunology)