Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer

TLDR

Therapeutic prostate‑specific antigen–targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC‑VF treatment was evaluated for safety and for prolongation of progression‑free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study. Eligible patients had minimally symptomatic castration‑resistant metastatic prostate cancer and PROSTVAC‑VF consists of two recombinant viral vectors encoding PSA and three immune costimulatory molecules (B7.1, ICAM‑1, LFA‑3), with a vaccinia prime followed by six fowlpox boosts, and patients were randomized 2:1 to PROSTVAC‑VF plus GM‑CSF or control empty vectors plus saline. At three years, PROSTVAC‑VF patients had a 44% reduction in death rate, an 8.5‑month longer median OS (25.1 vs 16.6 months), and a hazard ratio of 0.56 (95% CI 0.37–0.85), while PFS was similar between groups.

Abstract

Therapeutic prostate-specific antigen (PSA) -targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study.In total, 125 patients were randomly assigned in a multicenter trial of vaccination series. Eligible patients had minimally symptomatic castration-resistant metastatic prostate cancer (mCRPC). PROSTVAC-VF comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1, and LFA-3). Vaccinia-based vector was used for priming followed by six planned fowlpox-based vector boosts. Patients were allocated (2:1) to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor or to control empty vectors plus saline injections.Eighty-two patients received PROSTVAC-VF and 40 received control vectors. Patient characteristics were similar in both groups. The primary end point was PFS, which was similar in the two groups (P = .6). However, at 3 years post study, PROSTVAC-VF patients had a better OS with 25 (30%) of 82 alive versus 7 (17%) of 40 controls, longer median survival by 8.5 months (25.1 v 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and stratified log-rank P = .0061.PROSTVAC-VF immunotherapy was well tolerated and associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS in men with mCRPC. These provocative data provide preliminary evidence of clinically meaningful benefit but need to be confirmed in a larger phase III study.