Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
Massachusetts General Hospital, Boston, Massachusetts.
Clin Cancer Res. 2021 Mar 15;27(6):1623-1630. doi: 10.1158/1078-0432.CCR-20-4476. Epub 2021 Jan 15.
To investigate whether radium-223 increases peripheral immune responses to sipuleucel-T in men with bone-predominant, minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).
A total of 32 patients were randomized 1:1 in this open-label, phase II multicenter trial. Patients in the control arm received three sipuleucel-T treatments, 2 weeks apart. Those in the combination arm received six doses of radium-223 monthly, with sipuleucel-T intercalated between the second and fourth doses of radium-223. The primary endpoint was a comparison of peripheral antigen PA2024-specific T-cell responses (measured by proliferation index). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and PSA responses.
We enrolled 32 patients, followed for a median of 1.6 years. Six weeks after the first sipuleucel-T dose, participants in the control arm had a 3.2-fold greater change in PA2024-specific T-cell responses compared with those who received combination treatment ( = 0.036). Patients in the combination arm were more likely to have a >50% PSA decline [5 (31%) vs. 0 patients; = 0.04], and also demonstrated longer PFS [39 vs. 12 weeks; HR, 0.32; 95% confidence interval (CI), 0.14-0.76] and OS (not reached vs. 2.6 years; HR, 0.32; 95% CI, 0.08-1.23).
Our data raise the possibility of greater clinical activity with the combination of sipuleucel-T and radium-223 in men with asymptomatic bone mCRPC, despite the paradoxically lower immune responses observed. Additional study to confirm these findings in a larger trial is warranted.
探究镭-223 是否会增强骨骼为主、症状轻微的转移性去势抵抗性前列腺癌（mCRPC）患者对树突细胞-前列腺癌疫苗（sipuleucel-T）的外周免疫反应。
这是一项开放标签、2 期多中心试验，共纳入 32 例患者，1:1 随机分组。对照组患者每 2 周接受 3 次 sipuleucel-T 治疗，联合组患者每月接受 6 次镭-223 治疗，镭-223 第 2 次和第 4 次治疗之间插入 2 次 sipuleucel-T 治疗。主要终点为外周抗原 PA2024 特异性 T 细胞反应（增殖指数测定）的比较。次要终点为无进展生存期（PFS）、总生存期（OS）和 PSA 反应。
共纳入 32 例患者，中位随访 1.6 年。第 1 次 sipuleucel-T 治疗后 6 周，对照组患者的 PA2024 特异性 T 细胞反应较联合组增加 3.2 倍（ = 0.036）。联合组患者更有可能出现 PSA 下降>50%[5（31%）例 vs. 0 例； = 0.04]，且 PFS 更长[39 周 vs. 12 周；HR=0.32，95%CI：0.14-0.76]和 OS 更长（未达到 vs. 2.6 年；HR=0.32，95%CI：0.08-1.23）。
尽管观察到的免疫反应较低，但我们的数据提示，对于无症状骨骼 mCRPC 男性患者，sipuleucel-T 和镭-223 联合治疗可能具有更大的临床活性。需要更大规模的试验来证实这些发现。
