Axitinib and Long-Acting Octreotide in Advanced Extrapancreatic Neuroendocrine Tumors: A Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Trial (AXINET, GETNE 1107).

This study evaluates efficacy and safety of axitinib in extrapancreatic (ep)-NETs.

本研究评估了阿西替尼在胰腺外（ep）-NETs中的疗效和安全性。

patients_and_methods

AXINET was an international, randomized, double-blind, placebo-controlled, phase II/III trial including patients age 18 years and older, with unresectable/metastatic G1-2 epNETs and up to two previous treatment lines.

AXINET 是一项国际性的随机、双盲、安慰剂对照的 II/III 期临床试验，纳入年龄在 18 岁及以上的患者，这些患者患有不可切除/转移性 G1-2 级类癌（epNETs），并且最多接受过两线治疗。

Patients were randomly assigned (1:1) to axitinib 5 mg or placebo, both orally twice a day, in combination with intramuscular octreotide long-acting release 30 mg once every 28 days until disease progression or unacceptable toxicity.

患者按 1:1 的比例随机分配接受阿西替尼 5 mg 或安慰剂，均为口服，每日两次，与肌肉注射奥曲肽长效释放剂 30 mg 每 28 天一次联合使用，直至疾病进展或出现不可接受的毒性。

Randomization was stratified by primary tumor site, Ki-67 index (≤5% or >5%), and time from diagnosis (> or ≤12 months).

随机分组根据原发肿瘤部位、Ki-67指数（≤5%或>5%）以及诊断时间（>或≤12个月）进行了分层。

The primary end point was investigator-assessed progression-free survival(PFS).

主要终点是研究者评估的无进展生存（PFS）。

Efficacy was also assessed by a blinded independent central review (BICR).

疗效也通过盲法独立中央审查（BICR）进行评估。

Results

From October 2011 to May 2019, 256 patients were assigned to axitinib (n = 126) or placebo (n = 130).

从2011年10月到2019年5月，256名患者被分配到阿克替尼（n = 126）或安慰剂（n = 130）。

Investigator-assessed median PFS was 17.2 months (95% CI, 13.6 to 24.7) versus 13.1 months (95% CI, 10.9 to 18.6) in the axitinib and placebo groups, respectively (hazard ratio[HR], 0.86 [95% CI, 0.65 to 1.15]).

研究者评估的中位无进展生存期（PFS）在阿克替尼组和安慰剂组分别为17.2个月（95%置信区间，13.6至24.7个月）和13.1个月（95%置信区间，10.9至18.6个月）（风险比[HR]，0.86 [95%置信区间，0.65至1.15]）。

The median BICR PFS was 16.6 months (95% CI, 13.5 to 24.2) versus 9.9 months (95% CI, 8.2 to 13.9) in the axitinib and placebo groups, respectively (HR, 0.71 [95% CI, 0.54 to 0.94], P = .017).

独立评审委员会（BICR）评估的中位无进展生存期（PFS）在阿克替尼组和安慰剂组分别为16.6个月（95%置信区间，13.5至24.2个月）和9.9个月（95%置信区间，8.2至13.9个月）（风险比[HR]，0.71 [95%置信区间，0.54至0.94]，P = .017）。

Objective response rate(ORR) was significantly greater for axitinib per investigator assessment (17.5% v 4.6%; P = .001) and BICR (12.8% v 3.2%; P = .005).

根据研究者评估，阿克替尼的客观缓解率（ORR）显著更高（17.5%对比4.6%；P = .001），且独立评审委员会（BICR）评估也显示阿克替尼的ORR更高（12.8%对比3.2%；P = .005）。

Most common grade ≥3 toxicities were hypertension (24.0% v 9.2%) and diarrhea (13.6% v 1.5%).

最常见的3级或以上不良事件是高血压（24.0%对比9.2%）和腹泻（13.6%对比1.5%）。

Conclusions

Axitinib significantly increased PFS per BICR assessment and ORR both per investigator and BICR assessment compared with placebo, although the primary study end point was not met.

阿西替尼显著延长了基于独立评审委员会(BICR)评估的无进展生存期(PFS)和基于研究者及BICR评估的客观缓解率(ORR)，与安慰剂相比，尽管未达到主要研究终点。

Toxicity profile was manageable with no new safety concerns.

毒性特征是可管理的，没有出现新的安全问题。