The recent AUA meetings in Atlanta had a number of interesting abstracts presented that concern men with advanced prostate cancer. Some of the more interesting abstracts were look back analysis of sipuleucel-T (Provenge) done by consultants for Dendreon, the company who manufactures Provenge. They took the data from the al three of the phase III trials, including the IMPACT (IMunotherapy for Prostate Adeno Carcinoma Treatment) Trial that led to the eventual approval of Provenge by the FDA.
The two specific abstracts that were of personal interest were:

1- An analysis which evaluated the survival benefit associated with Provenge in African-American men who participated in the three phase III studies. Among the 737 men with metastatic castrate-resistant advanced prostate cancer, 488 were randomized to receive Provenge (African-American, 33; Caucasian, 437; other races, 18) and 249 were randomized to the control arm (African-American, 10; Caucasian, 229; other races, 10). They then performed a Cox proportional hazards regression analysis was used to assess the treatment effect on overall survival in all randomized patients and the African-American subpopulation.
The results of the African-American subgroup suggested a positive treatment effect (HR=0.288

[95% CI: 0.125, 0.662]; p=003). The exploratory analysis showed that African-American men treated with Provenge a had median overall survival benefit of 45.3 months versus 14.6 months in the control arm, a median survival difference of 30.7 months!

The abstract authors did point out and I wish to emphasize that due to the very small sample size no definitive conclusions can be made, but the results suggest that African-American men with metastatic castrate-resistant advanced prostate cancer benefit from treatment with Provenge. Clearly, due to the dramatic survival advantage being hinted at, there needs to be further investigation of this hypothesis. This conclusion was echoed by David McLeod, MD, of the Center for Prostate Disease Research, Uniformed Services University, Bethesda, MD.

2- The second Provenge abstract that I feel is of interest centered around the issue of crossover (Men who were in the control arm at disease progression were allowed to receive a frozen version of Provenge, APC8015F which was made at the time the control was manufactured.

Without any accounting for the crossover of men in the control arm the survival advantage for Provenge was 4.1 months. However, the question is what survival advantage did the administration of APC8015F have on the men in the control group, if any?

Using the assumption that APC8015F provides the same advantage that Provenge does the researchers found that the median overall survival benefit of Provenge in the phase III IMPACT trial was estimated to be 7.8 months, had there been no crossover to APC8015F (HR=0.60, 95% CI: 0.41, 0.95).

“This exploratory analysis provides important insight into how the crossover design of the IMPACT trial may have affected the overall survival findings,” said Leonard Gomella, MD, of the Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, who was first author of the crossover study. “These data support the use of Provenge as a foundation of care for the treatment of metastatic castrate-resistant prostate cancer.”

We can reasonably conclude that Provenge appears to demonstrate an overall survival benefit in men with advanced prostate cancer, perhaps giving a much better survival advantage then the original statistical analysis demonstrated. African-American men might actually benefit in a more dramatic number than others might.

Joel T. Nowak, M.A., M.S.W.