[镥]镥-多柔比星-奥曲肽在生长抑素受体阳性的胃肠胰神经内分泌肿瘤、嗜铬细胞瘤和副神经节瘤青少年患者中的安全性和剂量测定：II期NETTER-P研究的初步分析

Safety and dosimetry of [Lu]Lu-DOTA-TATE in adolescent patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours, or pheochromocytomas and paragangliomas: Primary analysis of the Phase II NETTER-P study.

作者信息

Gaze Mark N, Handkiewicz-Junak Daria, Hladun Raquel, Laetsch Theodore W, Sorge Caryn, Sparks Richard, Wan Simon, Ceraulo Antony, Kluczewska-Galka Aneta, Gámez-Cenzano Cristina, States Lisa J, El Khouli Riham, Aimone Paola, Perraud Kevin, Kollar Gabor, Khanshan Fariba, Blumenstein Lars, Brouri Fazia, Giraudet Anne-Laure

机构信息

Department of Oncology, University College London Hospitals NHS Foundation Trust, London, UK.

Maria Skłodowska-Curie Memorial National Research Institute of Oncology, Gliwice, Poland.

出版信息

Eur J Nucl Med Mol Imaging. 2025 Apr 8. doi: 10.1007/s00259-025-07246-7.

DOI:10.1007/s00259-025-07246-7

PMID:40198358

Abstract

PURPOSE

NETTER-P, an open-label Phase II study, evaluated the safety and dosimetry of [Lu]Lu-DOTA-TATE (hereafter Lu-DOTATATE) in adolescents with advanced, somatostatin receptor-positive, well-differentiated, Grade 1/2 gastroenteropancreatic neuroendocrine tumours (GEP-NET) or pheochromocytoma and paragangliomas (PPGL).

METHODS

Patients (12-17 years old) received four cycles of Lu-DOTATATE (7.4 GBq every 8 ± 1 weeks; cumulative administered activity: 29.6 GBq). Primary endpoints were absorbed dose (kidneys and bone marrow) and safety after first administration. Safety during treatment and comparative assessments of dosimetry and pharmacokinetics between adolescents and historical adult patients were evaluated.

RESULTS

Eleven patients (4 GEP-NET, 7 PPGL; median age 15 [range, 13-17] years) were enrolled and received ≥ 1 administration of Lu-DOTATATE. Median (range) cumulative administered activity was 28.2 (7.3-29.9) GBq. Lymphopenia/lymphocyte count decreased and headache were the most common adverse events (AEs) during Cycle 1 (each 4/11 [36%]). Cycle 1 Grade ≥ 3 AEs occurred in 4/11 patients (36%). During the treatment period, the most common AE was lymphopenia/lymphocyte count decreased (7/11 [64%]; Grade ≥ 3, 5/11 [45%]). No clinically meaningful impacts on safety biomarkers nor any treatment-related nephrotoxicities were observed. Projected median (range) cumulative absorbed doses (four administrations) were 21 (14-40) Gy in kidneys and 0.76 (0.55-1.0) Gy in bone marrow (using blood data). Dosimetry values were predicted to be within safety thresholds for adolescents and adults; pharmacokinetics were comparable in both populations.

CONCLUSION

No new safety signals attributable to Lu-DOTATATE were identified in adolescents with GEP-NET or PPGL versus adults with GEP-NET. Long-term follow-up is ongoing.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT04711135. Registered 15 January 2021.

摘要

目的

NETTER-P是一项开放标签的II期研究，评估了[镥]镥-多柔比星-奥曲肽（以下简称镥-奥曲肽）在患有晚期、生长抑素受体阳性、高分化的1/2级胃肠胰神经内分泌肿瘤（GEP-NET）或嗜铬细胞瘤和副神经节瘤（PPGL）的青少年中的安全性和剂量测定。

方法

患者（12至17岁）接受四个周期的镥-奥曲肽治疗（每8±1周7.4GBq；累积给药活度：29.6GBq）。主要终点是首次给药后的吸收剂量（肾脏和骨髓）和安全性。评估了治疗期间的安全性以及青少年与历史成年患者之间剂量测定和药代动力学的比较评估。

结果

11名患者（4例GEP-NET，7例PPGL；中位年龄15岁[范围，13至17岁]）入组并接受了≥1次镥-奥曲肽给药。中位（范围）累积给药活度为28.2（7.3至29.9）GBq。淋巴细胞减少/淋巴细胞计数下降和头痛是第1周期中最常见的不良事件（AEs）（各4/11[36%]）。4/11例患者（36%）发生了第1周期≥3级AE。在治疗期间，最常见的AE是淋巴细胞减少/淋巴细胞计数下降（7/11[64%]；≥3级，5/11[45%]）。未观察到对安全生物标志物有临床意义的影响，也未观察到任何与治疗相关的肾毒性。预计（范围）累积吸收剂量中位数（四次给药）肾脏为21（14至40）Gy，骨髓为0.76（0.55至1.0）Gy（使用血液数据）。预计青少年和成年人的剂量测定值均在安全阈值范围内；两个群体的药代动力学具有可比性。