Agent shows significant survival advantage in HRPC

Seattle-The prognosis for patients with advanced hormone-refractory prostate cancer is improving. That is the ultimate result from the latest trial of sipuleucel-T (Provenge), published last month (J Clin Oncol 2006; 24:3089-94). The novel immunotherapy agent showed a statistically significant survival advantage and a solid safety profile. Consequently, the manufacturer plans to submit trial data later this year as the basis for a biologics license application to the FDA.

"This trial holds a lot of promise," said study co-author Celestia S. Higano, MD, associate professor of medicine and urology at the University of Washington and the Seattle Cancer Care Alliance. "This is the first immunotherapy agent that has been shown to have a clinical benefit in hormone-refractory prostate cancer. If this product is approved, it will offer a treatment that is better tolerated than the chemotherapy agent docetaxel, the only other therapy we have that improves survival."

Sipuleucel-T may also offer more effective treatment. Median survival for sipuleucel-T-treated patients in this trial was 25.9 months versus 21.4 months for patients receiving placebo. That compares to 18.9 months and 17.5 months, respectively for patients receiving docetaxel versus placebo in recent trials of patients with hormone-refractory prostate cancer. The docetaxel trials included patients with a poorer prognosis; thus, the populations are not directly comparable.

The 36-month sipuleucel-T trial followed 127 patients with asymptomatic metastatic hormone-refractory prostate cancer. Men were randomized 2:1 to receive three infusions of sipuleucel-T or placebo at 2-week intervals. Placebo patients who showed disease progression could receive APC8015F, an open-label product made from frozen leukapheresis cells.

Phase I and II trials with sipuleucel-T showed declines in PSA levels of 50% or more in about 10% of patients. The phase III trial demonstrated clinical response.

All men in the trial progressed before death except one, who died of complications from a glioblastoma 6 months after treatment.

Men who received sipuleucel-T had a median survival time of 25.9 months, 4.5 months longer than the 21.4 months for those who received placebo (p=.01, log-rank; HR, 1.70; 95% CI, 1.13-2.56). The treatment arm showed an overall 41% reduction in the risk of death compared with men in the placebo arm. At the end of 36 months follow-up, 34% of men who received the drug were still alive, compared to 11% of men who received placebo.

Primary endpoint not met

Time to progression for men in the treatment arm was 11.7 weeks, a 31% improvement compared with 10 weeks for men in the placebo arm (p=.052, log-rank; HR, 1.45; 95% CI, .99-2.11). Men in the treatment arm also showed an eight-fold increase in T-cell immunity (16.9 vs. 1.99, p<.001), and treatment was very well tolerated.

That's the good news, Dr. Higano said. The bad news is that the improvement in time to progression, while good, was not statistically significant, which meant that the trial did not reach its primary endpoint.

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