To determine biomarkers predictive of overall survival (OS) in advanced cancer patients treated with a peptide-based cancer vaccine.
The samples from two randomized, double-blind, placebo-controlled, phase III trials of personalized peptide vaccine (PPV) for advanced prostate cancer patients (n = 306) and recurrent glioblastoma (n = 88) patients, those from one single arm phase II trial of PPV for various types of advanced cancer patients (n = 2588), and those from one randomized placebo-controlled non-personalized phase II trial (n = 51) were provided for this retrospective biomarker study.
No significant differences in clinical benefit (overall survival, OS) were found between the patients receiving PPV and those receiving placebo in each of the two randomized, double-blind, placebo-controlled, phase III trials. The neutrophil or lymphocyte proportion in advanced prostate cancer patients prior to study entry was a biomarker discriminating the PPV patients (70%) who showed significantly shorter OS relative to placebo patients from the remaining PPV patients who showed significantly longer OS relative to placebo patients. The CCL2 level prior to the study entry in recurrent glioblastoma patients was the other biomarker discriminating the PPV patients (40%) who showed significantly shorter OS relative to placebo patients from the remaining PPV patients who showed significantly longer OS relative to placebo patients. The neutrophil or lymphocyte proportion prior to study entry was also a biomarker discriminating the PPV patients (60%) with significantly shorter OS from the remaining PPV patients entered in the single arm phase II study in all the advanced cancer patients other than gastric cancer or glioblastoma patients. This marker could also discriminate patients who showed significantly shorter OS from the remaining patients in the non-personalized peptide vaccine phase II study for prostate cancer patients.
Peptide-based cancer vaccine shortened the OS of a large portion, but not all, of advanced cancer patients with various types of cancer. Prospective clinical studies of peptide-based cancer vaccines using the newly defined prognostic markers may be warranted.
UMIN Clinical Trials Registry, 6970, 113088, 11028, 1482, 1839, 1844, 1847, 1850, 1854, 1855, 1856, 1875, 1881, 1882, 1883, 1884, 2282, 3590, 5631, 6249, 6295, 6493, 7493, 8126, 8823, 8824, 8825, 8826, 8827, 8828, 10068, 19390, 2906, 2907, 2908, 2984, 2985, 2987, 3027, 3028, 3029, 3059, 3060, 3081, 3082, 3083, 5329, 10290, 11593, 14855, 19802, 19879, 6927,11230.
President Kyogo Itoh,M.D., Ph.D., Cancer vaccine center, Kurume University School of Medicine, Japan.
Grants from the Japan Agency for Medical Research and Development (16ck0106086h0003, 18im0110802h0008), the Ministry of Health, Labor and Welfare of Japan, and FUJIFILM Corporation.
M. Noguchi: Advisory / Consultancy: BrightPath Biotherapeutics Co. Ltd. A. Yamada: Advisory / Consultancy: BrightPath Biotherapeutics Co. Ltd. K. Itoh: Advisory / Consultancy, Research grant / Funding (self): Taiho Pharmaceutical Company. All other authors have declared no conflicts of interest.