A national multicenter phase 2 study of prostate-specific antigen (PSA) pox virus vaccine with sequential androgen ablation therapy in patients with PSA progression: ECOG 9802.

Abstract

BACKGROUND:

E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis.

OBJECTIVE:

To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden.

DESIGN, SETTING, AND PARTICIPANTS:

Patients who had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte-macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation.

RESULTS AND LIMITATIONS:

In step 1, 25 of 40 eligible patients (63%) were progression free at 6 mo after registration (90% confidence interval [CI], 48-75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p=0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade ≥4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57-87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study.

CONCLUSIONS:

A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients with minimal disease volume alone and combined with androgen ablation, supporting the feasibility of future phase 3 studies in this population.

PATIENT SUMMARY:

These data support consideration of vaccine therapy earlier in the course of prostate cancer progression with minimal disease burden in future studies of vaccine approaches in earlier stages of disease.

• Authors: Robert S DiPaola, Yu-Hui Chen, Glenn J Bubley, Mark N Stein, Noah M Hahn, Michael A Carducci, Edmund C Lattime, James L Gulley, Philip M Arlen, Lisa H Butterfield, George Wilding
• Journal: European urology (Eur Urol) Vol. 68 Issue 3 Pg. 365-71 (Sep 2015) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 25533418 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Association of Urology. All rights reserved.

Chemical References

• Androgen Antagonists
• Cancer Vaccines
• PROSTVAC
• Granulocyte-Macrophage Colony-Stimulating Factor
• KLK3 protein, human
• Kallikreins
• Prostate-Specific Antigen

Topics

• Aged
• Androgen Antagonists (therapeutic use)
• Cancer Vaccines (immunology, therapeutic use)
• Combined Modality Therapy
• Disease Progression
• Fowlpox virus (immunology)
• Granulocyte-Macrophage Colony-Stimulating Factor (therapeutic use)
• Humans
• Kallikreins (blood, immunology)
• Male
• Middle Aged
• Prostate-Specific Antigen (blood, immunology)
• Prostatectomy
• Prostatic Neoplasms (drug therapy)
• Vaccinia virus (immunology)