Duke University Medical Center, Durham, North Carolina.
University of Chicago, Chicago, Illinois.
Cancer Immunol Res. 2015 Sep;3(9):1063-9. doi: 10.1158/2326-6066.CIR-15-0006. Epub 2015 May 5.
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 III sipuleucel-T trials were offered, in nonrandomized 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 the effects of APC8015F on the overall survival (OS; Cox regression) of control-arm patients and treatment effects of sipuleucel-T versus control adjusted for APC8015F treatment [iterative parameter estimation model (IPE)]. The median time to first APC8015F infusion was 5.2 months (range, 1.8-33.1) after randomization and 2.2 months (0.5-14.6) after progression. After disease progression, median survival was longer for APC8015F-treated versus control-only treated patients [20.0 vs. 9.8 months; 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 status, age, and number of bone metastases as potential (P < 0.1) independent predictors of postprogression 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 versus 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 that APC8015F treatment may have extended patient survival, suggesting the sipuleucel-T OS advantage in CRPC may be more robust than previously estimated.
Sipuleucel-T 是一种用于治疗无症状/轻度症状转移性去势抵抗性前列腺癌（CRPC）的自体细胞免疫疗法。在疾病进展后，在三项双盲、随机 sipuleucel-T 试验的对照臂患者中，根据非随机开放标签方案接受了 APC8015F 治疗，APC8015F 是一种源自对照生产时冷冻保存细胞的自体免疫疗法。这些探索性分析评估了与这种治疗相关的生存结果的潜在影响。在 249 名接受对照治疗的患者中，有 165 名（66.3%）接受了 APC8015F 治疗。我们探讨了 APC8015F 对对照臂患者总生存（OS；Cox 回归）的影响，以及 sipuleucel-T 相对于 APC8015F 治疗调整后的对照治疗效果[迭代参数估计模型（IPE）]。首次 APC8015F 输注的中位时间为随机分组后 5.2 个月（范围为 1.8-33.1），进展后 2.2 个月（0.5-14.6）。疾病进展后，APC8015F 治疗组与仅对照治疗组患者的中位生存时间更长[20.0 个月比 9.8 个月；HR，0.53；95%置信区间（CI），0.38-0.74；P<0.001]；然而，APC8015F 治疗组患者的基线特征更为有利。多变量回归分析确定乳酸脱氢酶、碱性磷酸酶、血红蛋白、ECOG 状态、年龄和骨转移数量为疾病进展后生存的潜在（P<0.1）独立预测因素。在调整这些预测因素后，APC8015F（HR，0.78；95%CI，0.54-1.11；P=0.17）治疗趋势改善生存。如果 APC8015F 没有效果，调整 APC8015F 治疗后 sipuleucel-T 与对照的中位 OS 获益估计为 3.9 个月，如果 APC8015F 与 sipuleucel-T 同样有效，则为 8.1 个月。探索性分析表明，APC8015F 治疗可能延长了患者的生存时间，这表明 sipuleucel-T 在 CRPC 中的 OS 优势可能比之前估计的更为稳健。
