Subsequent treatment with APC8015F and its effect on survival in the control arm of phase III sipuleucel-t studies

• Published in: Journal of clinical oncology Vol. 29; no. 7_suppl; p. 139
• Main Authors: George, D. J., Nabhan, C., Gomella, L. G., Whitmore, J. B., Frohlich, M. W.
• Format: Journal Article
• Language: English
• Published: 01.03.2011
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2011.29.7_suppl.139

Abstract only 139 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for metastatic castrate resistant prostate cancer. Methods: After disease progression, subjects in the control arms of 3 randomized controlled sipuleucel-T trials were offered 3 infusions of APC8015F, an autologous immunotherapy made from cells cryopreserved at the time of control generation. Results: Of 249 control subjects, 165 (66.3%) received APC8015F; the median time from randomization to first infusion was 5.2 months (range 1.8 to 33.1), median time from objective disease progression to first APC8015F infusion was 2.2 months (range 0.5 to 14.6), and 145 subjects (87.9%) received all 3 infusions. The frequency of infusional toxicities was increased following APC8015F relative to control infusion, but was slightly lower than following sipuleucel-T. APC8015F-treated subjects (n=155) had improved post-progression survival relative to untreated controls (n=61) (HR=0.52 [95%CI 0.37, 0.73] p=0.0001, log rank test, unadjusted Cox regression); however, APC8015F-treated subjects had more favorable prognostic features than untreated controls. A Cox regression analysis adjusting for baseline PSA and LDH demonstrated that APC8015F therapy remained a predictor of survival in control subjects (HR=0.56 [95%CI 0.40, 0.80]; p=0.001). A Cox regression model adjusting for age, PSA, LDH and post-randomization docetaxel use (yes/no), also showed a significant effect for salvage treatment among control subjects (HR=0.55 [95%CI 0.39, 0.78] p<0.001). Examination of APC8015F product characteristics demonstrated that cumulative CD54 upregulation was associated with survival following first infusion in subjects who progressed and received APC8015F (p=0.03), consistent with previous reports of correlations between sipuleucel-T product parameters and overall survival. Conclusions: Although confounded with measured and unmeasured factors influencing outcome, these analyses suggest that post-progression treatment with APC8015F may have extended the survival of subjects in the control arms of these studies. [Table: see text]