Authors:
L. G. Gomella, C. Nabhan, J. B. Whitmore, M. W. Frohlich, & D. J. George
Summary:
Background - Sipuleucel-T is an autologous cellular immunotherapy approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.
Methods - After disease progression, subjects in the control arms of 3 randomized controlled trials (RCT) of sipuleucel-T were offered 3 infusions of APC8015F, an autologous immunotherapy made from cells cryopreserved at the time of control generation.
Results - 165/249 (66.3%) of the control group received APC8015F. Median time from randomization to first APC8015F infusion was 5.2 months (range 1.8 to 33.1), and from objective disease progression to first infusion was 2.2 months (range 0.5 to 14.6). 145 subjects (87.9%) received all 3 infusions. APC8015F-treated subjects had improved post-progression survival relative to untreated controls (HR = 0.52 [95% CI: 0.37, 0.73]; unadjusted Cox regression; P = 0.0001, log rank test), with median survival times of 20.0 and 9.8 months, respectively. APC8015F-treated subjects had more favorable prognostic features than untreated controls. To account for these differences, a Cox regression model was fit using backward selection, and included the following independent predictors of post-progression survival: lactate dehydrogenase, alkaline phosphatase, ECOG status, age, number of bone metastases, and hemoglobin. In addition, the model included post-randomization salvage treatment and docetaxel use as time dependent covariates. This analysis revealed a positive docetaxel effect (HR = 0.86 [95% CI: 0.60, 1.22]; P = 0.40), and a positive APCF8015F treatment effect (HR = 0.78 [95% CI: 0.54, 1.11]; P = 0.17). In subjects who received at least one infusion of APC8015F, the cumulative product lot release characteristics of CD54 upregulation and total nucleated cell counts were correlated with survival after salvage treatment (p=0.03 and p=0.04, respectively). Conclusions: Post-progression treatment with APC8015F may have extended survival of subjects, potentially reducing the magnitude of survival difference observed between sipuleucel-T and controls in RCT.
Source:
2011 American Society of Clinical Oncology Annual Meeting; Abstract No. 4534; Journal of Clinical Oncology; 29 (2011)