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Posted April 28, 2009

IMPACT: Sipuleucel-T vaccine increased OS

American Urological Association Annual Meeting

Today at the American Urological Association Annual Meeting, Paul Schellhammer, MD, professor of urology at Eastern Virginia Medical School, presented data from the phase-3 IMPACT trial that showed that sipuleucel-T, an experimental immunotherapy, significantly reduced the overall risk of death from prostate cancer.

In March 2007, the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee voted to recommend sipuleucel-T (Provenge, Dendreon) for FDA approval, after determining that the treatment for androgen-independent prostate cancer met safety and efficacy standards.

The committee voted 17-0 that the treatment met safety standards and 13-4 in favor of efficacy. In May 2007, the FDA ruled that more data were needed before the sipuleucel-T vaccine could be approved. This decision sparked protests from patients and advocates who urged the FDA to reverse its ruling.

Although the available data indicated the vaccine was safe, the standard for efficacy was not reached. Neither of the two small trials presented to the committee reached their primary endpoints of time to progression. Both trials showed better OS for patients treated with sipuleucel-T; however, this was not a planned primary or secondary endpoint for either trial. The benefit was identified during a follow-up analysis.

The trial presented at the AUA meeting was designed with a primary endpoint of OS. The multicenter, randomized, double blind study evaluated 500 men with asymptomatic or minimally symptomatic, metastatic, androgen-independent prostate cancer.

Compared with placebo, sipuleucel-T extended median survival by 4.1 months and improved three-year survival by 38%. The vaccine successfully exceeded the prespecified level of statistical significance defined by the study’s design and reduced the overall risk of death by 22.5% compared with placebo (P=.032).

The final results from the trial are expected in 2010. – by Leah Lawrence

These data are encouraging but are way too little information from which to draw any conclusions. A vaccine active in suppressing established human cancer has been long sought. Data from the sipuleucel trial are encouraging and the community of physicians who treat men with prostate cancer looks forward to seeing a full report.

– Donald L. Trump. MD

HemOnc Today Editorial Board member

In terms of whether these are the results everyone was hoping for, this study, as far as the results that were presented [at AUA], are in the ballpark of the results of the original phase-3 trial that was presented to the FDA a couple of years ago. Median survival was in the similar range and the researchers met their prespecified endpoints in terms of P value and hazard ratio. This would certainly be the results that both the company and the investigators were hoping for. With regards to whether or not this will be enough to get [the vaccine] approved, it's hard to know that offhand. On one level, this is the second phase-3 trial that is positive and met the prespecified goals. There will be some due diligence by the FDA to review the information, but assuming the data holds up to external review, I think it's very likely it would achieve FDA approval.

If one makes the assumption that it is approved and it is labeled in accord to the subpopulation of patients who were entered into the trial, the presumption would be that this is appropriate for patients who have evidence of progression in the castrate setting, who are relatively free of disease-related symptoms, and have not had chemotherapy for metastatic disease. Click here to hear Dr. Dreicer's perspective.

– Robert Dreicer, MD

ChairDepartment of Solid Tumor Oncology, Cleveland Clinic