Gomella, Leonard G.;
Nabhan, Chadi;
DeVries, Todd;
Whitmore, James Boyd;
Frohlich, Mark Walter;
George, Daniel J.
Impact of salvage therapy with APC8015F on the overall survival (OS) benefit achieved with sipuleucel-T in three phase III studies of metastatic castrate-resistant prostate cancer (mCRPC)
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Media type:
E-Article
Title:
Impact of salvage therapy with APC8015F on the overall survival (OS) benefit achieved with sipuleucel-T in three phase III studies of metastatic castrate-resistant prostate cancer (mCRPC)
Contributor:
Gomella, Leonard G.;
Nabhan, Chadi;
DeVries, Todd;
Whitmore, James Boyd;
Frohlich, Mark Walter;
George, Daniel J.
imprint:
American Society of Clinical Oncology (ASCO), 2012
Description:
<jats:p> e15120 </jats:p><jats:p> Background: Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic or minimally symptomatic mCRPC. Three phase III sipuleucel-T trials (D9901, D9902A and D9902B [IMPACT]) allowed control patients (pts) to receive salvage treatment with an autologous product derived from previously frozen cells (APC8015F). We previously reported that salvage therapy with APC8015F demonstrated no deleterious effect and may have improved outcomes in control pts, potentially reducing the observed survival benefit seen with sipuleucel-T. Thus, we performed an exploratory analysis of pooled data from phase III studies to estimate the impact of APC8015F treatment on the OS benefit conferred by sipuleucel-T. Methods: We analyzed the effect of salvage APC8015F therapy on OS, and used a rank-preserving structural failure time (RPSFT) model to estimate control arm OS if treatment with APC8015F had not occurred. This allows estimation of the effect of sipuleucel-T treatment on OS, adjusting for salvage effect. Results: Median OS from randomization in the three pooled trials was 25.4 months with sipuleucel-T (n=488) and 21.5 months with control (n=249). Of the control arm pts, 165 (66.3%) subsequently received APC8015F. Median OS from randomization in the control population was 23.6 months for pts receiving APC8015F and 12.7 months for those who did not. Using the RPSFT model, and assuming APC8015F was as effective as sipuleucel-T, the estimate of median OS for control pts was 17.3 months, representing an 8.1 month median increase in OS with sipuleucel-T. Results from extensions of the RPSFT model, where APC8015F is assumed to have less treatment effect than sipuleucel-T, will be presented. Conclusions: These analyses estimated a median OS benefit for sipuleucel-T between 3.9 and 8.1 months, assuming that APC8015F had either no efficacy or comparable efficacy to sipuleucel-T, respectively. The results suggest a possible greater treatment effect of sipuleucel-T than was reported in the three phase III studies. Future studies should account for potential crossover treatment bias as this may diminish estimates of OS benefit. </jats:p>