An investigational immunotherapy treatment improved overall survival by approximately 4 months in men with metastatic prostate cancer compared with men treated with a placebo, researchers reported last week at the American Urological Association annual meeting in Chicago. The results come from the IMPACT trial, a phase III, double-blind, randomized trial of sipuleucel-T (Provenge), a form of immunotherapy in which antigen-presenting cells are isolated from patients' blood, engineered to stimulate a tumor-specific immune response, and infused back into patients.

The more than 500 men in the trial had asymptomatic or minimally symptomatic, androgen-independent metastatic prostate cancer. In men who received sipuleucel-T, which was delivered in three infusions over a 1-month period, median survival was improved by 22.5 percent compared with men who received placebo (25.8 months versus 21.7 months). As was the case in the two earlier-stage trials of sipuleucel-T, there was no statistically significant improvement in progression-free survival, that is, survival without tumor growth.

Adverse events were minor and limited, said one of the trial's leaders, Dr. David Penson from the University of Southern California. The most common events were fever, chills, and headache the day after the infusion of sipuleucel-T, and these side effects typically resolved within a day or two. Overall, approximately 99 percent of patients in the immunotherapy arm received all three infusions.

The survival data were "incredibly consistent" in all of the subgroups examined in the trial, Dr. Penson explained, which included breakdowns by age, baseline PSA level, and extent of bone metastases, among others. "That is very reassuring to me," he said.

Dr. Penson acknowledged that, because of the trial's design, all patients in the immunotherapy arm could receive docetaxel immediately upon progression, unlike patients who received the placebo, and this could introduce bias in favor of sipuleucel-T. But the statistical model, he noted, was adjusted for both the use and timing of docetaxel administration. Further details of the data analysis should be available when the trial results are published in a scientific journal.

In March 2007, an FDA advisory committee recommended that sipuleucel-T be approved for men with this prostate cancer indication, based on data from two smaller clinical trials. In May 2007, however, the FDA issued a "complete response" letter to Dendreon, which manufactures sipuleucel-T, requesting more efficacy data before it could approve the company's application to market the treatment. According to Dendreon officials, the company will submit the IMPACT data to the FDA later this year as an amendment to its earlier marketing approval application.