Sipuleucel-T is an autologous cellular immunotherapy for asymptomatic/minimally symptomatic metastatic castrate-resistant prostate cancer (CRPC). After disease progression, control-arm patients on three double-blind, randomized phase 3 sipuleucel T trials were offered, in non-randomized open-label protocols, APC8015F, an autologous immunotherapy made from cells cryopreserved at the time of control manufacture. These exploratory analyses evaluated potential effects on survival outcomes associated with such treatment. Of 249 control-treated patients, 165 (66.3%) received APC8015F. We explored APC8015F's effects on control-arm overall survival (OS; Cox regression) and treatment effects of sipuleucel-T vs. control adjusted for APC8015F treatment (iterative parameter estimation model). Median time to first APC8015F infusion was 5.2 months (range: 1.8-33.1) post randomization and 2.2 months (0.5-14.6) post-progression. After disease progression, median survival was longer for APC8015F vs. control-only treated patients (20.0 vs. 9.8 months; hazard ratio [HR]=0.53 [95% confidence interval (CI): 0.38, 0.74]; P<0.001); however, baseline characteristics were more favorable for APC8015F treated patients. Multivariate regression analyses identified lactate dehydrogenase, alkaline phosphatase, hemoglobin, ECOG, age, and number of bone metastases as potential (P<0.1) independent predictors of post-progression survival. After adjusting for these predictors, APC8015F (HR=0.78 [95%CI: 0.54, 1.11]; p=0.17) treatment trended toward improved survival. Estimated median OS benefit for sipuleucel-T vs. control adjusted for APC8015F treatment was 3.9 months if APC8015F had no effect and was 8.1 months if APC8015F was equally as effective as sipuleucel-T. Exploratory analyses indicate APC8015F treatment may have extended patient survival, suggesting the sipuleucel-T OS advantage in CRPC may be more robust than previously estimated.
- Received January 11, 2015.
- Revision received March 19, 2015.
- Accepted April 13, 2015.
- Copyright © 2015, American Association for Cancer Research.