镭-223 治疗骨转移去势抵抗性前列腺癌三种剂量方案的随机 II 期临床试验。
A randomised phase II trial of three dosing regimens of radium-223 in patients with bone metastatic castration-resistant prostate cancer.
机构信息
Englander Institute for Precision Medicine, Weill Cornell Medical Center, New York, USA.
Montreal Cancer Institute, Montreal University Hospital Center (CHUM), Montreal, QC, Canada.
出版信息
Ann Oncol. 2020 Feb;31(2):257-265. doi: 10.1016/j.annonc.2019.10.025. Epub 2019 Dec 23.
BACKGROUND
Radium-223 prolongs overall survival and delays symptomatic skeletal events (SSEs) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. The approved radium-223 regimen is 55 kBq/kg every 4 weeks (q4w) for six cycles (standard dose). We investigated different radium-223 regimens in patients with mCRPC.
PATIENTS AND METHODS
Patients were randomised 1 : 1 : 1 to radium-223 standard-dose, high-dose (88 kBq/kg q4w for six cycles) or extended-schedule arms (55 kBq/kg q4w for 12 cycles). The primary end point, SSE-free survival (SSE-FS), was compared in patients treated with a high- versus standard-dose regimen, or with a standard dose in an extended (>6 to 12 cycles) versus standard schedule (six cycles).
RESULTS
A total of 391 patients were randomised; baseline characteristics were balanced between arms. On-treatment SSEs developed in 37/130 (28%), 42/130 (32%) and 48/131 (37%) patients in the standard-dose, high-dose and extended-schedule arms, respectively. There was no statistically significant difference in SSE-FS in the high- versus standard-dose arms [median 12.9 months versus 12.3 months; hazard ratio (HR) 1.06, 80% confidence interval (CI) 0.88-1.27, P = 0.70], and in the extended- versus standard-schedule arms (median 10.8 months versus 13.2 months; HR 1.26, 80% CI 0.94-1.69, P = 0.31). Overall survival in the three treatment arms was similar. As many as 370 (95%) patients received treatment (median of six cycles) in each arm. Grade ≥3 treatment-emergent adverse events (TEAEs) affected 34% of patients in the standard-dose, 48% in the high-dose and 53% in the extended-schedule arm, causing permanent discontinuation in 9%, 16% and 17% of patients, respectively.
CONCLUSION
Radium-223 high-dose or extended-schedule regimens resulted in no change in SSE-FS or other efficacy end points and were associated with more grade ≥3 TEAEs. The extended-schedule regimen (beyond six doses) could not be implemented in a large proportion of patients due to disease progression. Therefore, the standard-dose schedule remains one of the standard therapies for patients with symptomatic mCRPC.
TRIAL REGISTRATION
ClinicalTrials.govNCT02023697.
背景
镭-223 可延长转移性去势抵抗性前列腺癌（mCRPC）和骨转移患者的总生存期并延迟有症状骨骼事件（SSE）。已批准的镭-223 方案为每 4 周（q4w）55 kBq/kg，共 6 个周期（标准剂量）。我们研究了 mCRPC 患者的不同镭-223 方案。
患者和方法
患者以 1:1:1 的比例随机分为镭-223 标准剂量、高剂量（88 kBq/kg q4w，共 6 个周期）或延长方案组（55 kBq/kg q4w，共 12 个周期）。主要终点是 SSE 无进展生存期（SSE-FS），比较高剂量与标准剂量方案，或标准剂量延长方案（6 个周期以上至 12 个周期）与标准方案（6 个周期）。
结果
共纳入 391 例患者，各治疗组间基线特征均衡。在治疗期间，标准剂量、高剂量和延长方案组分别有 37/130（28%）、42/130（32%）和 48/131（37%）例患者发生 SSE。高剂量与标准剂量组间 SSE-FS 无统计学差异[中位值 12.9 个月比 12.3 个月；风险比（HR）1.06，80%置信区间（CI）0.88-1.27，P=0.70]，延长方案与标准方案组间也无差异[中位值 10.8 个月比 13.2 个月；HR 1.26，80%CI 0.94-1.69，P=0.31]。三组的总生存期相似。每个治疗组均有 370（95%）例患者接受了治疗（中位 6 个周期）。标准剂量、高剂量和延长方案组分别有 34%、48%和 53%的患者发生≥3 级治疗相关不良事件（TEAEs），分别有 9%、16%和 17%的患者因 TEAEs 而永久停药。
结论
高剂量或延长方案的镭-223 治疗并未改善 SSE-FS 或其他疗效终点，且与更多的≥3 级 TEAEs 相关。由于疾病进展，大多数患者无法接受延长方案（6 个剂量以上）。因此，标准剂量方案仍是有症状 mCRPC 患者的标准治疗之一。
临床试验注册
ClinicalTrials.govNCT02023697。
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