Special Report: Vaccines for the Treatment of Prostate Cancer*
Executive Summary
Background
Vaccines for the treatment of prostate cancer have been under development. Several types of vaccines have been tested in patients, and a few have reached the point where Phase III clinical trials have been undertaken. At this point in time, there are no prostate cancer vaccines approved by the U.S. Food and Drug Administration (FDA)**. The intent of a prostate cancer vaccine is to effectively prime the patient's immune system against prostate cancer antigens and stimulate an immune response against tumor cells. Current trials of prostate cancer vaccines have mostly enrolled patients with asymptomatic metastatic androgen-independent prostate cancer, but some studies have examined the use of vaccines as an adjuvant to treatment for localized prostate cancer.
Objective
The objectives of this Special Report are informational in nature, as follows:
* to describe the various biologic approaches being taken to develop a prostate cancer vaccine
* to describe the specific products that have reached at least Phase II randomized studies
* to review the results of completed Phase III trials of prostate cancer vaccines
Search Strategy
The MEDLINE® database (via PubMed) was searched through August 2009. The search strategy included the terms "prostate cancer," "vaccine*" (truncated), "immunotherapy," "dendritic" OR "antigen*" (truncated). ClinicalTrials.gov was also searched in September 2009 to identify agents that were in at least Phase II randomized studies to focus the literature search.
Selection Criteria
Data on prostate cancer vaccines in development were included if they were in at least Phase II randomized trials that were completed, were in progress, or were registered, as noted on the ClinicalTrials.gov website. Data from completed Phase III randomized trials were also included.
Main Results
Several types of vaccines are currently under development for the treatment of prostate cancer. The current indication for most of the vaccines appears to be the asymptomatic but recurrent cancer patient with androgen-independent disease. Such a patient can be treated with docetaxel with a survival benefit, but currently most patients defer such treatment until symptomatic, as the drug has adverse effects but is still effective in symptomatic patients.
Sipuleucel-T (Provenge®) has reached the most advanced state of study, and shows a possibly curious result that it does not prevent cancer progression, but is associated with increased overall survival. The current Phase III trial so far has reported an overall survival benefit. In this trial and the prior smaller Phase III trials of sipuleucel-T, most patients who progressed went on to receive chemotherapy. According to analyses examining this chemotherapy treatment, this was not a confounding factor, but this will need to be examined carefully in the current Phase III trial of sipuleucel-T and other vaccine trials. The Phase II trial of ProstVAC-VF apparently shows a similar finding so far in interim analyses, with a sole finding of an increased overall survival, even though survival was not the primary endpoint of the study.
Author's Conclusions and Comments
Other than sipuleucel-T and ProstVAC-VF, other types of vaccines are much less advanced in the types of clinical investigations that have been carried out. These other vaccines still await the initiation and completion of Phase II randomized trials. The prognosis of the current indication of these vaccine products is a median survival between 20 and 30 months. Demonstration of a survival benefit among candidate patients at earlier stages of disease would require much longer periods of study due to the greater baseline prognosis of these patients. However, without such studies, it would be premature to extend the indications for such vaccines (if any are proven to be effective for the current indication).
*This Special Report is a summary of the background for and an evidence-based analysis of the Phase II or III clinical trial data of prostate cancer vaccine therapy. It does not attempt to address the question as to whether the TEC criteria are met.
**On April 29, 2010, the FDA approved Provenge® (sipuleucel-T, Dendreon, Inc.) for "the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer." FDA News Release: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm210174.htm
Full Study
Special Report: Vaccines for the Treatment of Prostate Cancer
Full studies are in PDF format. You will need Adobe Acrobat Reader to view all studies.
Download Adobe Acrobat Reader here.
androgen; androgen-independent; antigen-based; asymptomatic; BCG; cellular; chemotherapy; co-stimulatory; dendritic; DNA; docetaxel; estramustine; GM-CSF; GVAX; hormone; hormone-refractory; hormone-resistant; immunologic; immunology; immunotherapy; interleukin 2; membrane; metastasis; metastatic; mitoxantrone; Onyvax; PAP; peptide; Phase II; Phase III; phosphatase; prednisone; prostate-specific antigen; prostein; ProstVAC; ProstVAC-VF; Provenge; PSA; PSMA; pTVG-HP; pulsed; refractory; sipuleucel-T; survivin; TARP; telomerase; vaccine; vaccine; vaccinia; viral; VITAL; whole-cell;
