683 ESTIMATING THE OVERALL SURVIVAL BENEFIT OF SIPULEUCEL-T IN THE IMPACT TRIAL ACCOUNTING FOR CROSSOVER TREATMENT IN CONTROL SUBJECTS WITH AUTOLOGOUS IMMUNOTHERAPY GENERATED FROM CYROPRESERVED CELLS

Abstract

You have accessJournal of UrologyProstate Cancer: Advanced I1 Apr 2012683 ESTIMATING THE OVERALL SURVIVAL BENEFIT OF SIPULEUCEL-T IN THE IMPACT TRIAL ACCOUNTING FOR CROSSOVER TREATMENT IN CONTROL SUBJECTS WITH AUTOLOGOUS IMMUNOTHERAPY GENERATED FROM CYROPRESERVED CELLS Leonard Gomella, Chadi Nabhan, Todd DeVries, James Whitmore, Mark Frohlich, and Daniel George Leonard GomellaLeonard Gomella Philadelphia, PA More articles by this author , Chadi NabhanChadi Nabhan Park Ridge, IL More articles by this author , Todd DeVriesTodd DeVries Seattle, WA More articles by this author , James WhitmoreJames Whitmore Seattle, WA More articles by this author , Mark FrohlichMark Frohlich Seattle, WA More articles by this author , and Daniel GeorgeDaniel George Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.765AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Sipuleucel-T, an autologous cellular immunotherapy produced from each patient's freshly isolated immune cells, is approved for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer. In the pivotal IMPACT trial, control subjects who demonstrated objective disease progression were offered 3 infusions of an autologous cellular therapy (APC8015F) produced from cells frozen at the time of control product generation. An exploratory analysis was performed to estimate how APC8015F impacted the overall survival (OS) benefit of sipuleucel-T in the IMPACT study. METHODS A rank-preserving structural failure time (RPSFT) model was applied to account for the effect of APC8015F and to estimate the treatment effect of sipuleucel-T relative to control had no crossover to APC8015F occurred. RESULTS In the IMPACT study (n=512), there was a 4.1-month improvement in median OS (25.8 vs. 21.7 months) for sipuleucel-T compared with control (HR=0.78; 95% CI: 0.61, 0.98; p=0.032). 109/171 (64%) of control patients received APC8015F; other post-progression interventions were similar. The frequency of acute infusion toxicities was greater following APC8015F than control, but lower than sipuleucel-T. Median OS was 23.8 months for control patients receiving APC8015F and 11.6 months for patients not receiving APC8015F. Median APC8015F cumulative CD54 upregulation, a measure of APC activation, was 22.2 and was similar to the 28.7-fold increase with sipuleucel-T. Controlling for some of the known prognostic factors at the time of progression, the treatment effect persists, suggesting APC8015F may have extended survival of control subjects. Using the RPSFT model, and assuming APC8015F was equally as effective as sipuleucel-T, the estimate of median OS for control would be 18.0 months, representing a 7.8 month improvement in median OS in favor of sipuleucel-T (HR=0.60, 95% CI: 0.41, 0.96). Results from the RPSFT model that assumed a lesser treatment effect of APC8015F will be presented. CONCLUSIONS Post-progression treatment with APC8015F may have extended the survival of control subjects in the IMPACT study. Adjusting for use of APC8015F resulted in an increase in median OS benefit with sipuleucel-T of up to 7.8 months. These results suggest a greater treatment effect of sipuleucel-T than reported in IMPACT, and should be factored into future studies without APC8015F crossover. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e278-e279 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Leonard Gomella Philadelphia, PA More articles by this author Chadi Nabhan Park Ridge, IL More articles by this author Todd DeVries Seattle, WA More articles by this author James Whitmore Seattle, WA More articles by this author Mark Frohlich Seattle, WA More articles by this author Daniel George Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...