Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
Clin Cancer Res. 2019 Dec 1;25(23):6939-6947. doi: 10.1158/1078-0432.CCR-19-1026. Epub 2019 Aug 22.
Radiolabeled somatostatin receptor 2 (SSTR2) antagonists have shown higher tumor uptake and tumor-to-organ ratios than somatostatin agonists in preclinical models of neuroendocrine tumors (NETs). We performed a phase I study to evaluate the safety and efficacy of SSTR2 antagonist Lu-satoreotide tetraxetan.
Twenty patients with advanced SSTR2-positive NETs were treated with Lu-satoreotide tetraxetan. Patients first underwent a dosimetry study with Lu-satoreotide tetraxetan to determine the therapeutic activity that could be safely administered. This activity was split into two equal cycles to be delivered 3 months apart. The maximum activity was 7.4 GBq per cycle.
Of 20 patients with NETs (one lung, seven small bowel, nine pancreatic, one gastric, one rectal, one kidney; mean prior treatments: three), six received one cycle of Lu- satoreotide tetraxetan and 14 received two cycles. Hematologic toxicity after cycle 1 was mild-moderate and reversed before cycle 2. However, grade 4 hematologic toxicity occurred in four of seven (57%) patients after cycle 2 of Lu-satoreotide tetraxetan. The study was suspended, and the protocol modified to limit the cumulative absorbed bone marrow dose to 1 Gy and to reduce prescribed activity for cycle 2 by 50%. The best overall response rate was 45% [5% complete response (1/20), 40% partial response (8/20)]; with 40% stable disease (8/20) and 15% progression of disease (3/20). Median progression-free survival (PFS) was 21.0 months (95% CI, 13.6-NR).
In this trial of heavily treated NETs, preliminary data are promising for the use of Lu-satoreotide tetraxetan. Additional studies are ongoing to determine optimal therapeutic dose/schedule.
在神经内分泌肿瘤（NET）的临床前模型中，放射性标记的生长抑素受体 2（SSTR2）拮抗剂比生长抑素激动剂显示出更高的肿瘤摄取率和肿瘤与器官的比率。我们进行了一项 I 期研究，以评估 SSTR2 拮抗剂 Lu-satoreotide tetraxetan 的安全性和疗效。
20 例晚期 SSTR2 阳性 NET 患者接受 Lu-satoreotide tetraxetan 治疗。患者首先进行 Lu-satoreotide tetraxetan 剂量测定研究，以确定可安全给予的治疗活性。该活性分为两个相等的周期，相隔 3 个月进行。最大活性为每个周期 7.4GBq。
20 例 NET 患者（1 例肺，7 例小肠，9 例胰腺，1 例胃，1 例直肠，1 例肾；中位既往治疗：3 种）中，6 例接受了 1 个周期的 Lu-satoreotide tetraxetan 治疗，14 例接受了 2 个周期。第 1 周期后血液学毒性为轻度至中度，并在第 2 周期前逆转。然而，Lu-satoreotide tetraxetan 第 2 周期后，7 例患者中有 4 例（57%）发生 4 级血液学毒性。研究暂停，方案修改为限制累积骨髓吸收剂量至 1Gy，并将第 2 周期的规定活性降低 50%。最佳总体缓解率为 45%[5%完全缓解（1/20），40%部分缓解（8/20）]；40%疾病稳定（8/20），15%疾病进展（3/20）。中位无进展生存期（PFS）为 21.0 个月（95%CI，13.6-NR）。
在这项针对 NET 的大量治疗的试验中，Lu-satoreotide tetraxetan 的初步数据令人鼓舞。正在进行额外的研究以确定最佳治疗剂量/方案。
