Nivolumab ± Ipilimumab in Patients With Pretreated Advanced Neuroendocrine Carcinoma: The GCO-001 NIPINEC Randomized Phase II Trial.

This study aimed to investigate the efficacy of nivolumab ± ipilimumab.

本研究旨在探讨纳武利尤单抗±伊匹木单抗的疗效。

Methods

The GCO-001-NIPINEC (ClinicalTrials.gov identifier: NCT03591731) trial was a noncomparative, open-label, phase II trial. The main inclusion criteria were age ≥18 years, performance status (PS) ≤2, advanced large- and small-cell GEP-NEC and large-cell lung NEC, and second- or third-line treatment for NECs refractory to platinum-based chemotherapy.

GCO-001-NIPINEC试验（ClinicalTrials.gov注册号：NCT03591731）是一项非比较性、开放标签的II期试验。主要纳入标准为年龄≥18岁，体能状态（PS）≤2，晚期大细胞和小细胞GEP-NEC以及大细胞肺癌NEC，并且为对铂类化疗耐药的NECs的二线或三线治疗。

Patients were randomly assigned (1:1) and stratified by age and PS to receive nivolumab (3 mg/kg/once every 2 weeks) ± ipilimumab (1 mg/kg/once every 6 weeks) for 2 years or until progression or unacceptable toxicity.

患者按1:1的比例随机分配，并根据年龄和PS分层，接受每两周一次的nivolumab（3 mg/kg）±每六周一次的ipilimumab（1 mg/kg），持续两年或直至疾病进展或出现不可接受的毒性。

The primary end point was objective response rate(ORR) at 8 weeks, assessed by investigators.

主要终点是研究者在8周时评估的客观缓解率（ORR）

Results

A total of 185 patients (91 in the nivolumab arm and 94 in the nivolumab-ipilimumab arm) were enrolled between December 2018 and March 2021; 169 were analyzed (median age of 64.5 years, 71% male, 91% PS 0-1).

共有185名患者（其中91名在纳武单抗组，94名在纳武单抗-伊匹木单抗组）在2018年12月至2021年3月期间入组；分析了169名患者（中位年龄为64.5岁，71%为男性，91%的PS评分为0-1）

The main primary tumor locations were lungs (50%), colorectal (15%), gastroesophageal (14%), and pancreatic (13%) regions.

主要的原发肿瘤部位是肺部（50%）、结直肠（15%）、胃食管（14%）和胰腺（13%）区域。

The ORR at 8 weeks was 7.2% (95% CI, 2.7 to 15.1]) in the nivolumab arm and 14.0% (95% CI, 7.4 to 23.1) in the nivolumab-ipilimumab arm.

在第8周时，纳武利尤单抗组的客观缓解率（ORR）为7.2%（95%置信区间，2.7至15.1），而纳武利尤单抗-伊匹木单抗组的ORR为14.0%（95%置信区间，7.4至23.1）。

The best ORR was 9.6% and 20.9%, respectively, whereas the median progression-free and overall survivalwere approximately 2 months and 6 months in both arms.

最佳客观缓解率(ORR)分别为9.6%和20.9%，而两组的中位无进展生存期和总生存期分别约为2个月和6个月。

One treatment-related death occurred, in the nivolumab arm.

在纳武单抗组中发生了一例与治疗相关的死亡。

The grade 3-4 adverse events (≥5%) were asthenia (13%), gamma-glutamyl transferase increase (10%), alkaline phosphatase increase (9%), dyspnea (7%), and anemia (6%) in the nivolumab-ipilimumab arm.

在纳武单抗-伊匹木单抗组中，3-4级不良事件（发生率≥5%）包括乏力（13%）、γ-谷氨酰转移酶升高（10%）、碱性磷酸酶升高（9%）、呼吸困难（7%）和贫血（6%）。

Conclusions

Nivolumab-ipilimumab could be a second-/third-line treatment option for patients with NECs.

对于患有神经内分泌癌（NECs）的患者，纳武单抗-伊匹木单抗可能是一个二线/三线治疗选择。

However, given the limited magnitude of benefit, studies are warranted to evaluate its use earlier and/or associated with chemotherapy.

然而，鉴于其益处有限，有必要进行研究以评估其早期使用和/或与化疗联合使用的有效性。