Lancet:[177Lu]Lu-DOTA-泰特联合长效奥曲肽与高剂量长效奥曲肽治疗新诊断的2-3级晚期高分化胃肠胰神经内分泌肿瘤(NETTER-2)的比较:一项开放性随机III期研究

1天前 来源:Lancet

本文由小咖机器人翻译整理

期刊来源:Lancet

原文链接:https://doi.org/10.1016/S0140-6736(24)00701-3

摘要内容如下:

背景

对于更高级别的2-3级、分化良好的晚期胃肠胰神经内分泌肿瘤患者,目前尚无标准的一线治疗方案。我们旨在研究[177Lu]Lu-DOTA-Tate(177Lu-DOTATate)一线治疗的有效性和安全性。

方法

NETTER-2是一项开放标签、随机、平行组、优势、3期试验。我们纳入了来自北美、欧洲和亚洲9个国家45个中心的新诊断为高2级(Ki67≥10%且≤20%)和3级(Ki67>20%且≤55%)、生长抑素受体阳性(在所有靶病变中)、晚期胃肠胰神经内分泌肿瘤的患者(年龄≥15岁)。我们使用交互反应技术随机分配(2:1)患者接受4个周期(周期间隔为8周±1周)静脉注射177Lu-DOTATATE和肌肉注射奥曲肽30 mg长效可重复(LAR),然后每4周注射奥曲肽30 mg LAR(177Lu-DOTATATE组)或每4周注射高剂量奥曲肽60 mg LAR(对照组),根据神经内分泌肿瘤分级(2 vs 3)和起源(胰腺vs其他)进行分层。在基线、第16周和第24周进行肿瘤评估,然后每12周进行一次评估,直到疾病进展或死亡。主要终点是通过盲法、独立、中心放射学评估的无进展生存期。我们对101个无进展生存事件进行了初步分析,作为最终的无进展生存分析。Netter-2在ClinicalTrials.gov,NCT03972488上注册,并且是活跃的,没有招募。

调查结果

在2020年1月22日至2022年10月13日期间,我们筛选了261名患者,其中35名(13%)被排除。我们将226名(87%)患者(121名[54%]男性和105名[46%]女性)随机分配到177Lu-DOTATATE组(n=151[67%])和对照组(n=75[33%])。对照组的中位无进展生存期为8.5个月(95%CI为7.7~13.8),177Lu-DOTATAT组的中位无进展生存期为22.8个月(未估计19.4个月)(分层风险比0.276[0.18 2~0.418];P<0.0001)。在治疗期间,177Lu-DOTATATE组的147名接受治疗的患者中有136名(93%)和对照组的73名接受治疗的患者中有69名(95%)发生了不良事件(任何级别)。在治疗期间,没有与药物相关的研究死亡。

解释

在2级或3级晚期胃肠胰神经内分泌肿瘤患者中,一线177Lu-DOTATATE联合奥曲肽LAR显著延长了中位无进展生存期(14个月)。177Lu-DOTATATE应被视为该人群一线治疗的新标准。

英文原文如下:

Abstracts

BACKGROUND  There are currently no standard first-line treatment options for patients with higher grade 2-3, well-differentiated, advanced, gastroenteropancreatic neuroendocrine tumours. We aimed to investigate the efficacy and safety of first-line [177Lu]Lu-DOTA-TATE (177Lu-Dotatate) treatment.

METHODS  NETTER-2 was an open-label, randomised, parallel-group, superiority, phase 3 trial. We enrolled patients (aged ≥15 years) with newly diagnosed higher grade 2 (Ki67 ≥10% and ≤20%) and grade 3 (Ki67 >20% and ≤55%), somatostatin receptor-positive (in all target lesions), advanced gastroenteropancreatic neuroendocrine tumours from 45 centres across nine countries in North America, Europe, and Asia. We used interactive response technologies to randomly assign (2:1) patients to receive four cycles (cycle interval was 8 weeks ± 1 week) of intravenous 177Lu-Dotatate plus intramuscular octreotide 30 mg long-acting repeatable (LAR) then octreotide 30 mg LAR every 4 weeks (177Lu-Dotatate group) or high-dose octreotide 60 mg LAR every 4 weeks (control group), stratified by neuroendocrine tumour grade (2 vs 3) and origin (pancreas vs other). Tumour assessments were done at baseline, week 16, and week 24, and then every 12 weeks until disease progression or death. The primary endpoint was progression-free survival by blinded, independent, central radiology assessment. We did the primary analysis at 101 progression-free survival events as the final progression-free survival analysis. NETTER-2 is registered with ClinicalTrials.gov, NCT03972488, and is active and not recruiting.

FINDINGS  Between Jan 22, 2020, and Oct 13, 2022, we screened 261 patients, 35 (13%) of whom were excluded. We randomly assigned 226 (87%) patients (121 [54%] male and 105 [46%] female) to the 177Lu-Dotatate group (n=151 [67%]) and control group (n=75 [33%]). Median progression-free survival was 8·5 months (95% CI 7·7-13·8) in the control group and 22·8 months (19·4-not estimated) in the 177Lu-Dotatate group (stratified hazard ratio 0·276 [0·182-0·418]; p<0·0001). During the treatment period, adverse events (of any grade) occurred in 136 (93%) of 147 treated patients in the 177Lu-Dotatate group and 69 (95%) of 73 treated patients in the control group. There were no study drug-related deaths during the treatment period.

INTERPRETATION  First-line 177Lu-Dotatate plus octreotide LAR significantly extended median progression-free survival (by 14 months) in patients with grade 2 or 3 advanced gastroenteropancreatic neuroendocrine tumours. 177Lu-Dotatate should be considered a new standard of care in first-line therapy in this population.

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