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A randomized phase III trial of personalized peptide vaccination for castration?resistant prostate cancer progressing after docetaxel.

ABSTRACT: First?line chemotherapy for men with metastatic castration?resistant prostate cancer (mCRPC) has been employed to improve overall survival (OS) and progression?free survival (PFS). However, several new agents for CRPC after first?line chemotherapy prolonged survival by only a few months. To develop a new treatment modality, we conducted a phase III randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)?A24?positive patients with castration?resistant prostate cancer (CRPC) for whom docetaxel chemotherapy failed. This randomized, double?blind, placebo?controlled, phase III trial was carried out at 68 medical centers in Japan. Patients were randomly assigned at a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on pre?existing peptide?specific immunoglobulin G levels or the corresponding placebo were subcutaneously injected in 6 doses weekly and then bi?weekly following the maximum of 30 doses until disease progression. The primary end?point was overall survival (OS). Efficacy analyses were performed by the full analysis set. Between August 2013 and April 2016, 310 patients were randomly assigned, and 306 patients were analyzed. Baseline characteristics were balanced between groups. The estimated median OS was 16.1 months [95% confidence interval (CI), 13?18.2] with PPV and 16.9 months (95% CI, 13.1?20.4) with placebo [hazard ratio (HR), 1.04, 95% CI, 0.80?1.37; P=0.77]. Grade ?3 adverse events were observed in 41% of both groups. The analysis of treatment arm effects among subgroups revealed lower HRs for OS in favor of the PPV arm in patients with <64% neutrophils (HR, 0.55, 95% CI, 0.33?0.93; P=0.03) or ?26% lymphocytes (HR, 0.70, 95% CI, 0.52?0.92; P=0.02) at baseline. PPV did not prolong OS in HLA?A24?positive patients with CRPC progressing after docetaxel chemotherapy. Subgroup analysis suggested that the patients with a lower proportion of neutrophils or a higher proportion of lymphocytes at baseline can receive survival benefits from PPV treatment.

SUBMITTER: Noguchi M

PROVIDER: S-EPMC7709822 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A randomized phase III trial of personalized peptide vaccination for castration‑resistant prostate cancer progressing after docetaxel.

Noguchi Masanori M Fujimoto Kiyohide K Arai Gaku G Uemura Hiroji H Hashine Katsuyoshi K Matsumoto Hiroaki H Fukasawa Satoshi S Kohjimoto Yasuo Y Nakatsu Hideomi H Takenaka Atsushi A Fujisawa Masato M Uemura Hirotsugu H Naito Seiji S Egawa Shin S Fujimoto Hiroyuki H Hinotsu Shiro S Itoh Kyogo K

Oncology reports 20201111 1

First‑line chemotherapy for men with metastatic castration‑resistant prostate cancer (mCRPC) has been employed to improve overall survival (OS) and progression‑free survival (PFS). However, several new agents for CRPC after first‑line chemotherapy prolonged survival by only a few months. To develop a new treatment modality, we conducted a phase III randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)‑A24‑positive patients with castration‑resistant prostate ...[more]

PMID: 33200227

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Project description:BackgroundThe optimal sequencing of the multiple active agents now available for metastatic castration-resistant prostate cancer (mCRPC) is unclear. Prior reports have suggested diminished responses to sequential lines of androgen receptor (AR)-targeted therapies, but it is unknown whether subsequent taxane-based chemotherapy may be more effective than sequential AR-targeting treatment. We sought to evaluate the clinical activity of enzalutamide versus docetaxel in men with mCRPC who progressed on abiraterone.MethodsWe performed a single-institution retrospective analysis of consecutive mCRPC patients who had progressed on abiraterone therapy and subsequently received either enzalutamide (n=30) or docetaxel (n=31). We evaluated clinical outcomes including prostate-specific antigen decline of >30% (PSA30) or >50% (PSA50), PSA-progression-free survival (PSA-PFS), and clinical/radiographic PFS. We performed multivariable modeling to control for baseline and on-treatment differences between groups.ResultsCompared to subjects who received enzalutamide post-abiraterone, subjects who received docetaxel post-abiraterone had more bone metastases, more visceral metastases, higher baseline PSA, and had more frequent PSA tests while on-treatment. There were no significant differences in PSA30 (41% for enzalutamide vs. 53% for docetaxel) or PSA50 (34% vs. 40%) response rates between the two groups; there remained no difference after stratifying by presence/absence of prior response to abiraterone. Median PSA-PFS was 4.1 versus 4.1 months for the enzalutamide and docetaxel cohorts, respectively (HR 1.35, 95% CI, 0.53-3.66, P=0.502). Median PFS was 4.7 versus 4.4 months, respectively (HR 1.44, 95% CI, 0.77-2.71, P=0.257). PSA-PFS and PFS did not differ after stratifying by prior response to abiraterone. In multivariable analyses, there were no significant differences in PSA-PFS or PFS between the two groups.ConclusionsTreatment with either enzalutamide or docetaxel produced modest PSA responses and PFS intervals in this abiraterone-pretreated mCRPC population. In this retrospective study with small sample size, no significant differences in outcomes were observed between groups. Therefore, either enzalutamide or docetaxel may be a reasonable option in men who have progressed on abiraterone.

Dataset Information

A randomized phase III trial of personalized peptide vaccination for castration?resistant prostate cancer progressing after docetaxel.

Publications

A randomized phase III trial of personalized peptide vaccination for castration‑resistant prostate cancer progressing after docetaxel.

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