Yao James C, Strosberg Jonathan, Fazio Nicola, Pavel Marianne E, Bergsland Emily, Ruszniewski Philippe, Halperin Daniel M, Li Daneng, Tafuto Salvatore, Raj Nitya, Campana Davide, Hijioka Susumu, Raderer Markus, Guimbaud Rosine, Gajate Pablo, Pusceddu Sara, Reising Albert, Degtyarev Evgeny, Shilkrut Mark, Eddy Simantini, Singh Simron
J Yao, Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
J Strosberg, GI Oncology, Moffitt Cancer Center, Tampa, United States.
Endocr Relat Cancer. 2021 Jan 1. doi: 10.1530/ERC-20-0382.
Spartalizumab, a humanized anti-programmed death protein 1 (PD-1) monoclonal antibody, was evaluated in patients with well-differentiated metastatic grade 1/2 neuroendocrine tumors (NET) and poorly-differentiated gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC). In this phase II, multicenter, single-arm study, patients received spartalizumab 400 mg every 4 weeks until confirmed disease progression or unacceptable toxicity. The primary endpoint was confirmed overall response rate (ORR) according to blinded independent review committee using response evaluation criteria in solid tumors 1.1. The study enrolled 95 patients in the NET group (30, 32 and 33 in the thoracic, gastrointestinal, and pancreatic cohorts, respectively), and 21 patients in the GEP-NEC group. The ORR was 7.4% (95% confidence interval [CI]: 3.0, 14.6) in the NET group (thoracic, 16.7%; gastrointestinal, 3.1%; pancreatic, 3.0%), which was below the predefined success criterion of ≥10%, and 4.8% (95% CI: 0.1, 23.8) in the GEP-NEC group. In the NET and GEP-NEC groups, the 12-month progression-free survival was 19.5% and 0%, respectively, and the 12-month overall survival was 73.5% and 19.1%, respectively. The ORR was higher in patients with ≥1% PD-L1 expression in immune/tumor cells or ≥1% CD8+ cells at baseline. The most common adverse events considered as spartalizumab-related included fatigue (29.5%) and nausea (10.5%) in the NET group, and increased aspartate and alanine aminotransferases (each 14.3%) in the GEP-NEC group. The efficacy of spartalizumab was limited in this heterogeneous and heavily pre-treated population; however, the results in the thoracic cohort is encouraging and warrants further investigation. Adverse events were manageable and consistent with previous experience.
斯巴他利珠单抗是一种人源化抗程序性死亡蛋白1（PD-1）单克隆抗体，在高分化1/2级转移性神经内分泌肿瘤（NET）和低分化胃肠胰神经内分泌癌（GEP-NEC）患者中进行了评估。在这项II期、多中心、单臂研究中，患者每4周接受400mg斯巴他利珠单抗治疗，直至确认疾病进展或出现不可接受的毒性。主要终点是根据盲法独立审查委员会使用实体瘤疗效评价标准1.1确定的总缓解率（ORR）。该研究纳入了95例NET组患者（胸段、胃肠道和胰腺队列分别为30例、32例和33例）以及21例GEP-NEC组患者。NET组的ORR为7.4%（95%置信区间[CI]：3.0，14.6）（胸段为16.7%；胃肠道为3.1%；胰腺为3.0%），低于预先设定的≥10%的成功标准，GEP-NEC组的ORR为4.8%（95%CI：0.1，23.8）。在NET组和GEP-NEC组中，12个月无进展生存率分别为19.5%和0%，12个月总生存率分别为73.5%和19.1%。基线时免疫/肿瘤细胞中PD-L1表达≥1%或CD8+细胞≥1%的患者ORR更高。被认为与斯巴他利珠单抗相关的最常见不良事件包括NET组中的疲劳（29.5%）和恶心（10.5%），以及GEP-NEC组中的天冬氨酸和丙氨酸转氨酶升高（均为14.3%）。在这个异质性高且接受过大量预处理的人群中，斯巴他利珠单抗的疗效有限；然而，胸段队列的结果令人鼓舞，值得进一步研究。不良事件可控，且与以往经验一致。
