PROSTVAC™ in scientific publications
Overall Survival Analysis of a Phase II Randomized
Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in
Metastatic Castration-Resistant Prostate Cancer
J Clin Oncol. 2010 Jan 25
PURPOSE: 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. PATIENTS AND
METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Immunologic and prognostic factors associated with
overall survival employing a poxviral-based PSA vaccine in
metastatic castrate-resistant prostate cancer
Cancer Immunology, Immunotherapy
A concurrent multicenter, randomized Phase II trial employing a
recombinant poxviral vaccine provided evidence of enhanced median
overall survival (OS) (p = 0.0061) in patients with metastatic
castrate-resistant prostate cancer (mCRPC). The study reported here
employed the identical vaccine in mCRPC to investigate the
influence of GM-CSF with vaccine, and the influence of immunologic
and prognostic factors on median OS. Thirty-two patients were
vaccinated once with recombinant vaccinia containing the transgenes
for prostate-specific antigen (PSA) and three costimulatory
molecules. Patients received boosters with recombinant fowlpox
containing the same four transgenes. Twelve of 32 patients showed
declines in serum PSA post-vaccination and 2/12 showed decreases in
index lesions. Median OS was 26.6 months (predicted median OS by
the Halabi nomogram was 17.4 months). Patients with greater
PSA-specific T-cell responses showed a trend (p = 0.055) toward
enhanced survival. There was no difference in T-cell responses or
survival in cohorts of patients receiving GM-CSF versus no GM-CSF.
Patients with a Halabi predicted survival of <18 months (median
predicted 12.3 months) had an actual median OS of 14.6 months,
while those with a Halabi predicted survival of ≥18 months
(median predicted survival 20.9 months) will meet or exceed 37.3
months, with 12/15 patients living longer than predicted (p =
0.035). Treg suppressive function was shown to decrease following
vaccine in patients surviving longer than predicted, and increase
in patients surviving less than predicted. This
hypothesis-generating study provides evidence that patients with
more indolent mCRPC (Halabi predicted survival ≥18 months) may
best benefit from vaccine therapy.
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Prostvac-VF: a vector-based vaccine targeting PSA in
prostate cancer
Expert Opinion on Investigational Drugs, Volume 18, Issue 7
2009
Prostvac is a prostate cancer vaccine regimen consisting of a
recombinant vaccinia vector as a primary vaccination, followed by
multiple booster vaccinations employing a recombinant fowlpox
vector. Both vectors contain the transgenes for prostate-specific
antigen (PSA) and multiple T-cell co-stimulatory molecules
(TRICOM). The PSA-TRICOM vaccines infect antigen-presenting cells
(APCs) and generate proteins that are expressed on the surface of
the APCs in an immune context. The interaction of these APCs with T
cells initiates a targeted immune response and T cell-mediated
tumor cell destruction. Preliminary clinical trials have indicated
negligible toxicity, and Phase II trials have suggested a survival
benefit after treatment with Prostvac, especially in patients with
indolent disease characteristics. Preclinical and clinical data
indicate that radiation, hormonal therapy, and chemotherapy may be
combined with Prostvac to enhance the vaccine's efficacy.
Additional strategies are in development to further enhance the
clinical benefits of Prostvac, and a Phase III trial is being
planned in metastatic castration-resistant prostate cancer.
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