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

作者：DiPaola Robert S^*; Chen Yu Hui; Bubley Glenn J; Stein Mark N; Hahn Noah M; Carducci Michael A; Lattime Edmund C; Gulley James L; Arlen Philip M; Butterfield Lisa H; Wilding George

来源：European Urology, 2015, 68(3): 365-371.

DOI：10.1016/j.eururo.2014.12.010

• Prostate cancer
• Pox virus
• Vaccine
• PSA

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 6mo 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 withandrogenablation, supporting the feasibility of futurephase 3studies in thispopulation.
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.

• 出版日期2015-9
• 单位rutgers