医脉通编译，转载请务必注明出处

2016年6月3-7日，一年一度的美国临床肿瘤学会（American Society of Clinical Oncology，ASCO）年会在芝加哥举办。6月6日上午的消化系统（非结直肠）肿瘤口头报告专场上，一项摘要号为4005的NETTER-1 III期试验，对中肠神经内分泌肿瘤患者接受¹⁷⁷Lu-DOTATATE治疗的疗效和安全性结果进行评估，医脉通整理如下：

接受一线生长抑素类似物治疗的晚期中肠神经内分泌肿瘤（NETs）患者进展后，可以选择的治疗方案有限。这项III期试验的目的是评估¹⁷⁷Lu-DOTA⁰-Tyr³-Octreotate（Lutathera）治疗晚期，进展的sstr阳性中肠NETs的疗效和安全性。

230例1-2级转移性中肠NETs患者被随机接受Lutathera，每8周7.4GBq（×4给药）vs长效奥曲肽60mg每4周。主要终点是PFS（根据RECIST 1.1）联合每12周的肿瘤评估。次要目标包括ORR，OS，毒性和QoL。

在意向治疗人群（ITT）中，Lutathera的中位PFS未达到，对照组为8.4个月（P＜0.0001，HR 0.21）。在Lutathera组，确认23例疾病进展或死亡，长效奥曲肽组有67例进展或死亡。Lutathera组的客观放射反应率（ORR）为18%，对照组为3%（P=0.0008）。除了核素¹¹¹铟-喷曲肽肿瘤摄取评分（Krenning规模≥2）外，在Cox回归模型中，肿瘤负荷和Ki67等级对临床疗效预后（PFS，OS，TTP）没有显著影响。中期OS分析（Lutathera组13例死亡，对照组22例死亡，P=0.019）强烈显示OS有所改善。只有5%（6例）患者接受Lutathera表现出剂量调整毒性。中性粒细胞减少，血小板减少和淋巴细胞减少的3或4级不良事件分别在Lutathera组1%，2%和9%的患者中发生，对照组中没有出现上述不良事件。

NETTER-1试验提供了具有临床意义的证据而且PFS和ORR出现了统计学上的显著增加，这提示在ITT和PP分析中晚期中肠NETs患者接受Lutathera的潜在生存获益。此外，Lutathera的安全性被发现非常有利。临床试验信息：NCT01578239。

会议专题》》》2016年ASCO年会专题报道

原文摘要：

NETTER-1 phase III: Efficacy and safety results in patients with midgut neuroendocrine tumors treated with 177Lu-DOTATATE.(Abstract 4005)

Authors：Jonathan R. Strosberg, Edward M. Wolin,et al.

Session Type：Oral Abstract Session

Background: There are limited therapeutic options for patients with advanced midgut NETs progressing on first-line somatostatin analog therapy. The purpose of this phase III trial was to evaluate the efficacy and safety of 177Lu-DOTA0-Tyr3-Octreotate (Lutathera) in patients with advanced, progressive sstr positive midgut NETs.

Methods: 230 patients with grade 1-2 metastatic midgut NETs were randomized to Lutathera, 7.4 GBq every 8 weeks (x 4 administrations) vs Octreotide LAR 60 mg every 4 weeks. Primary endpoint was PFS (RECIST 1.1) with tumor assessment every 12 weeks. Secondary objectives included ORR, OS, toxicity and QoL.

Results: In the intent-to-treat population (ITT), the median PFS was not reached for Lutathera and was 8.4 months with control (p < 0.0001, HR 0.21). There were 23 centrally confirmed disease progressions or deaths in the Lutathera arm and 67 in the Octreotide LAR 60 mg arm. The objective radiographic response rate (ORR) was 18% with Lutathera and 3% with control (p = 0.0008). Besides the scintigraphic 111In-pentetreotide tumor uptake score (Krenning scale > = 2), tumor burden and Ki67 grade had no significant effect on clinical efficacy outcomes (PFS, OS, TTP) in the Cox regression models. Interim OS analysis (13 deaths in Lutathera group and 22 in control group; p = 0.019) strongly suggests an improvement in OS. Only 5% (6 patients) experienced dose modifying toxicity with Lutathera. Grade 3 or 4 adverse events of neutropenia, thrombocytopenia and lymphopenia occurred in 1%, 2% and 9% of patients in Lutathera arm vs. none in controls.

Conclusions: The NETTER-1 trial provides evidence for a clinically meaningful and statistically significant increase in PFS and ORR, and suggests a potential survival benefit in patients with advanced midgut NETs treated with Lutathera in both ITT and PP analyses. Lutathera safety profile was found to be very favorable. Clinical trial information: NCT01578239

打开微信 →→ 添加“医脉通肿瘤科”公众号，或扫描电脑屏幕右上方二维码 →→ 关注医脉通肿瘤科。随时随地获取肿瘤前沿资讯，一次打包最实用的肿瘤治疗知识。做科研达人、临床高手，尽在医脉通肿瘤频道。