[177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial.

The COMPETE trial evaluated the efficacy and harms of peptide receptor radionuclide therapy ([177Lu]Lu-edotreotide) versus targeted molecular therapy (everolimus) in patients with advanced, progressive, somatostatin receptor-positive GEP NETs.

COMPETE试验评估了肽受体放射性核素治疗（[177Lu]Lu-edotreotide）与靶向分子治疗（everolimus）在晚期、进展性、生长抑素受体阳性GEP NETs患者中的疗效和危害。

Methods

This phase 3, open-label, superiority trial included patients aged 18 years or older with treatment-naive or previously treated unresectable or metastatic (or both) grade 1-2 GEP NETs.

这项第三阶段、开放标签、优效试验纳入了18岁或以上的患者，这些患者要么是未接受过治疗的，要么是之前接受过治疗的，患有不可切除的或转移性的（或两者兼有）1-2级胃肠道神经内分泌肿瘤（GEP NETs）。

Patients were enrolled from 49 specialist neuroendocrine tumour treatment centres across 14 countries in Africa, Europe, North America, and Oceania and randomised (2:1) to intravenous [177Lu]Lu-edotreotide (7·5 ± 0·7 GBq every 3 months, maximum four cycles) or oral everolimus (10 mg/day) for up to 30 months.

患者从非洲、欧洲、北美和大洋洲的14个国家的49个神经内分泌肿瘤专业治疗中心入组，并按2:1的比例随机分配接受静脉注射[177Lu]Lu-edotreotide（每3个月7.5 ± 0.7 GBq，最多四个周期）或口服依维莫司（每天10 mg），最长治疗时间为30个月。

Random assignment was via a central, web-based randomisation system (block size of 6) and stratified by primary tumour origin and previous therapy.

随机分配是通过一个中央的、基于网络的随机化系统（块大小为6）进行的，并根据原发肿瘤的起源和之前的治疗进行分层。

The primary endpoint was progression-free survival, assessed via blinded independent central review in all randomly assigned patients at 30 months.

主要终点是无进展生存期，通过在所有随机分配的患者中进行30个月的盲法独立中央审查来评估。

Harms were assessed in all enrolled patients who received at least one dose of a study drug.

在所有接受至少一次研究药物剂量的入组患者中评估了不良反应。

This study was registered with ClinicalTrials.gov (NCT03049189) and is no longer recruiting.

该研究已在ClinicalTrials.gov注册（NCT03049189），目前不再招募新患者。

Results

Between April 13, 2017, and June 20, 2022, 324 patients were enrolled and 309 patients (including 168 [54%] male patients and 141 [46%] female patients) were randomly assigned to treatment: 207 to the [177Lu]Lu-edotreotide group and 102 to the everolimus group.

2017年4月13日至2022年6月20日期间，共有324名患者入组，其中309名患者（包括168名[54%]男性患者和141名[46%]女性患者）被随机分配接受治疗：207名患者分配至[177Lu]Lu-edotreotide组，102名患者分配至everolimus组。

The median follow-up for progression-free survivalwas 27·5 months (IQR 19·6-30·4) for the [177Lu]Lu-edotreotide group and 21·2 months (8·9-29·4) for the everolimus group.

无进展生存期的中位随访时间为[177Lu]Lu-edotreotide组27.5个月（四分位数间距19.6-30.4个月），everolimus组为21.2个月（四分位数间距8.9-29.4个月）。

Median progression-free survivalwas significantly longer with [177Lu]Lu-edotreotide versus everolimus (23·9 months [95% CI 18·7-30·0] vs 14·1 months [9·2-20·9]; stratified hazard ratio0·67 [95% CI 0·48-0·95]; p=0·022).

与依维莫司相比，[177Lu]Lu-edotreotide的中位无进展生存期显著更长（23.9个月 [95% 置信区间 18.7-30.0] 对比 14.1个月 [95% 置信区间 9.2-20.9]；分层风险比为0.67 [95% 置信区间 0.48-0.95]；p=0.022）。

Treatment-related adverse events occurred in 178 (82%) of 217 patients in the [177Lu]Lu-edotreotide group and 96 (97%) of 99 patients in the everolimus group. 40 (18%) patients in the [177Lu]Lu-edotreotide group and 40 (40%) in the everolimus group had at least one treatment-related grade 3-4 adverse event.

在[177Lu]Lu-edotreotide组的217名患者中，有178名（82%）出现了与治疗相关的不良事件，而在依维莫司组的99名患者中，有96名（97%）出现了与治疗相关的不良事件。在[177Lu]Lu-edotreotide组中有40名（18%）患者和在依维莫司组中有40名（40%）患者至少出现了一次与治疗相关的3-4级不良事件。

The most common treatment-related adverse events in the [177Lu]Lu-edotreotide group were diarrhoea and nausea (both 79 [36%] patients) and asthenia (66 [33%] patients), whereas those in the everolimus group were diarrhoea (45 [45%] patients), asthenia (36 [36%] patients), and anaemia (27 [27%] patients).

在[177Lu]Lu-edotreotide组中，最常见的与治疗相关的不良事件是腹泻和恶心（均为79[36%]患者），其次是乏力（66[33%]患者），而在everolimus组中，最常见的不良事件是腹泻（45[45%]患者）、乏力（36[36%]患者）和贫血（27[27%]患者）。

No treatment-related deaths occurred in either study group.

在两个研究组中均未发生与治疗相关的死亡事件。

interpretation

[177Lu]Lu-edotreotide led to statistically significant and clinically meaningful improvements in progression-free survival. Efficacy and harms results support the use of [177Lu]Lu-edotreotide in early lines of therapy in patients with advanced, progressive GEP NETs.

[177Lu]Lu-奥曲肽在无进展生存期上带来了统计学上显著且具有临床意义的改善。

funding

ITM Solucin.

ITM Solucin。