Safety and response after peptide receptor radionuclide therapy with 177Lu-DOTATATE for neuroendocrine tumors in phase 1/2 prospective Japanese trial
Safety and response after peptide receptor radionuclide therapy with 177Lu-DOTATATE for neuroendocrine tumors in phase 1/2 prospective Japanese trial
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DOI：
10.1002/jhbp.1101
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发表时间：
2021-12-27
影响因子：
3
通讯作者：
Kinuya, Seigo
中科院分区：
文献类型：
--
作者：
Kudo, Atsushi;Tateishi, Ukihide;Kinuya, Seigo
本前瞻性I/II期研究旨在阐明Lu-177-DOTATATE（4个周期，7.4 GBq）在日本不可切除的进行性神经内分泌肿瘤（NET）患者中的疗效和安全性。方法2018年4月至2020年10月，入组了15例晚期NETs患者（5例中肠、8例胰腺和2例肺NETs）。评价了客观缓解率（ORR）、无进展生存期（PFS）和不良事件（AE）。还在三名中肠患者中评价了药代动力学和剂量学。结果Lu-177-DOTATATE对肾脏和骨髓的平均吸收剂量分别为20.7戈伊/29.6 GBq和0.631戈伊/29.6 GBq，均在放射耐受剂量范围内。整个人群的ORR为53%（90% CI，30%-76%）。中肠和非中肠NET的ORR分别为60%（90% CI，19%-92%）和50%（90% CI，22%-78%）。中肠和非中肠NET患者的靶病变直径总和的最大缩小率无差异。未达到中位PFS; 52周时的PFS率为80%（90% CI，56.1%-91.7%）。3级或以上AE为淋巴细胞减少症（47%）和白细胞减少症（7%）。结论Lu-177-DOTATATE在日本晚期NETs患者中显示出显著的肿瘤缩小和耐受性。
Background The present prospective phase 1/2 study aimed to elucidate the efficacy and safety of Lu-177-DOTATATE (four cycles of 7.4 GBq) in Japanese patients with unresectable, progressive neuroendocrine tumors (NETs). Methods From April 2018 to October 2020, 15 patients with advanced NETs (five midgut, eight pancreatic, and two lung NETs) were enrolled. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were evaluated. Pharmacokinetics and dosimetry were also evaluated in three midgut patients. Results The mean absorbed doses of Lu-177-DOTATATE to the kidneys (20.7 Gy/29.6 GBq) and the bone marrow (0.631 Gy/29.6 GBq) were within the radiation tolerance doses. The ORR of the whole population was 53% (90% CI, 30%-76%). ORRs of the midgut and non-midgut NETs were 60% (90% CI, 19%-92%) and 50% (90% CI, 22%-78%), respectively. There was no difference in the maximum reduction rate of the sum of the target lesion diameters between patients with midgut and non-midgut NET. The median PFS was not reached; the PFS rate at 52 weeks was 80% (90% CI, 56.1%-91.7%). AEs of Grade 3 or higher were lymphopenia (47%) and leukopenia (7%). Conclusion Lu-177-DOTATATE demonstrated remarkable tumor shrinkage and tolerability in Japanese patients with advanced NETs.