Predictors of outcome and subgroup results from the integrated analysis of sipuleucel-T trials in metastatic castration-resistant prostate cancer.

Abstract

4550 Background: Sipuleucel-T is an investigational autologous active cellular immunotherapy for treatment of metastatic castration resistant prostate cancer. Reported here is an analysis of the homogeneity of the sipuleucel-T treatment effect across studies and within subgroups, and of predictors of overall survival (OS) in this population. Methods: OS for 3 randomized, double blind, placebo controlled trials was analyzed using a Cox regression model with treatment, adjusted for baseline PSA (ln) and LDH (ln), stratified by study. >20 subgroups were assessed using the same model with the addition of subgroup main effect and subgroup by treatment interaction terms. Continuous subgroup variables were dichotomized based on median value. Predictors of OS were identified using a multivariate Cox regression model. Results: The integrated analysis included 737 randomized patients (488 sipuleucel-T: 249 placebo) with median follow-up of 36 months. There was a significant sipuleucel-T treatment effect (HR=0.735, 95% CI:0.613, 0.882, P <0.001), which was found to be homogeneous across the 3 trials (study by treatment interaction P=0.66). A positive treatment effect (HR<1) was observed in all subgroups representing ≥10% of patients, including those defined by age, race, ECOG performance status, number of bone metastases, and previous chemotherapy use. Independent baseline predictors of OS in this patient population included ECOG status, number of bone metastases, nodal disease, age, weight, PSA, LDH, hemoglobin, and time from diagnosis to randomization. Alkaline phosphatase, Gleason sum, and prostatectomy were significantly associated with OS, but were not identified as independent predictors. Conclusions: The integrated analysis of 3 sipuleucel-T trials revealed consistent results across trials and within subgroups. The identification of ECOG status, PSA, LDH, and hemoglobin as significant predictors of OS in this population is consistent with those identified previously (Halabi 2003, Armstrong 2007) ; however, the identification of number of bone metastases, age, weight, nodal disease, and time from diagnosis to randomization represent new findings. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dendreon Dendreon Dendreon Dendreon Dendreon FDA