II 期临床试验证明了基于个体化剂量测定的 Lu-DOTATATE 治疗神经内分泌肿瘤患者的疗效和安全性。
Phase II trial demonstrates the efficacy and safety of individualized, dosimetry-based Lu-DOTATATE treatment of NET patients.
机构信息
Department of Clinical Sciences, Oncology and Pathology, Skåne University Hospital, Lund University, Lund, Sweden.
Department of Medical Radiation Physics, Clinical Sciences Lund, Lund University, Lund, Sweden.
出版信息
Eur J Nucl Med Mol Imaging. 2022 Sep;49(11):3830-3840. doi: 10.1007/s00259-022-05786-w. Epub 2022 Apr 22.
PURPOSE
Radionuclide therapy with Lu-DOTATATE is well established for patients with advanced somatostatin receptor-positive neuroendocrine tumors with a standard schedule of 7.4 GBq at four occasions. However, this approach does not consider individual variability affecting the tumor radiation dose or dose to organs at risk. Therefore, it is important to assess more personalized strategies. The aim of this phase II trial was to evaluate individualized Lu-DOTATATE for which the number of cycles varied based on renal dosimetry.
METHODS
Patients were eligible if they had a progressive, somatostatin receptor-positive neuroendocrine tumor with a Ki 67 labeling index < 20%. They received cycles of 7.4 GBq of Lu-DOTATATE at 10 ± 2-week intervals until a predefined radiation dose to the kidneys was reached. The primary endpoint was objective tumor response (RECIST v 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity (CTCAE v. 4.0).
RESULTS
Ninety-six patients who had received a median of 5 cycles (range 1-9) were evaluable for efficacy. The objective tumor response was 16% partial response, 66% stable disease, and 19% progressive disease. The median PFS and OS were 29 months and 47 months, respectively, and were significantly associated with kidney dose, performance status, and Ki 67 levels but not with tumor origin. The overall toxicity was mild, and the most common events were grade 1-2 anemia, thrombocytopenia, fatigue, nausea, and diarrhea. Grade 3-4 toxicity occurred in < 10% of patients and was mostly hematological, with no grade 3-4 renal toxicity.
CONCLUSION
Individualized treatment with Lu-DOTATATE based on renal dosimetry is clearly feasible with low toxicity and promising efficacy, showing the potential to further improve outcome beyond the standard approach, and should be further assessed in randomized trials.
TRIAL REGISTRATION
EudraCT 2011-000,240-16. NCT01456078. https://clinicaltrials.gov/ct2/show/NCT01456078.
目的
用 Lu-DOTATATE 进行放射性核素治疗对于晚期生长抑素受体阳性神经内分泌肿瘤患者是有效的，标准方案为每 4 周给予 7.4GBq，共 4 次。然而，这种方法没有考虑到影响肿瘤辐射剂量或靶器官剂量的个体差异。因此，评估更个性化的策略非常重要。本 II 期试验的目的是评估个体化的 Lu-DOTATATE，其周期数根据肾剂量测定而变化。
方法
如果患者患有进行性、生长抑素受体阳性神经内分泌肿瘤，且 Ki 67 标记指数 < 20%，则符合入组条件。他们每 10 ± 2 周接受 7.4GBq 的 Lu-DOTATATE 治疗，直到达到预设的肾脏辐射剂量。主要终点是客观肿瘤反应（RECIST v 1.1）。次要终点包括无进展生存期（PFS）、总生存期（OS）和毒性（CTCAE v. 4.0）。
结果
96 例患者接受了中位数为 5 个周期（范围 1-9 个）的治疗，可评估疗效。客观肿瘤反应为 16%部分缓解，66%疾病稳定，19%疾病进展。中位 PFS 和 OS 分别为 29 个月和 47 个月，与肾脏剂量、体能状态和 Ki 67 水平显著相关，但与肿瘤起源无关。总体毒性较轻，最常见的事件是 1-2 级贫血、血小板减少、疲劳、恶心和腹泻。< 10%的患者发生 3-4 级毒性，主要是血液学毒性，无 3-4 级肾毒性。
结论
基于肾剂量测定的个体化 Lu-DOTATATE 治疗显然是可行的，且毒性低、疗效好，显示出有潜力在标准治疗方法的基础上进一步提高疗效，应在随机试验中进一步评估。
试验注册
EudraCT 2011-000,240-16。NCT01456078。https://clinicaltrials.gov/ct2/show/NCT01456078。
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