Prostate cancer immunotherapy improves overall survival

The autologous cellular immunotherapy sipuleucel-T (Provenge) appears to demonstrate an overall survival benefit in patients with advanced prostate cancer, according to two studies presented at the AUA annual meeting in Atlanta.

An exploratory analysis evaluated the survival benefit associated with sipuleucel-T in African-American men who participated in the three sipuleucel-T phase III studies, including the IMPACT (IMunotherapy for Prostate AdenoCarcinoma Treatment) trial. Among 737 patients with metastatic castrate-resistant prostate cancer, 488 were randomized to receive sipuleucel-T (African-American, 33; Caucasian, 437; other races, 18) and 249 were randomized to the control arm (African-American, 10; Caucasian, 229; other races, 10). 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 sipuleucel-T 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.

While no definitive conclusions can be drawn given the limited sample size, the results suggest that African-American patients with metastatic castrate-resistant prostate cancer benefit from treatment with sipuleucel-T and provide support for further investigation of this hypothesis, said the researchers, led by David McLeod, MD, of the Center for Prostate Disease Research, Uniformed Services University, Bethesda, MD.

Separately, the IMPACT trial included a crossover design that allowed patients who were randomized to the control arm and experienced disease progression to participate in an open-label phase II protocol to receive APC8015F, an investigational autologous cellular immunotherapy made from cells that were cryopreserved at the time the control was manufactured.

In an exploratory analysis of the IMPACT trial, researchers used a rank-preserving structural failure time (RPSFT) model to quantify how treatment with APC8015F might have impacted the overall survival of the phase III IMPACT trial by adjusting for the positive treatment effect of APC8015F in the control arm. The previously published intent-to-treat analysis did not account for crossover and demonstrated a 4.1-month median survival benefit (HR=0.775, 95% CI: 0.614, 0.979).

Using the RPSFT model and assuming that APC8015F was equally effective as sipuleucel-T, the median overall survival benefit of sipuleucel-T 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."

Dr. Gomella is a consultant/adviser for Dendreon Corp.

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