Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, People's Republic of China.
Department of Oncology, The First Affiliated Hospital of the Medical School of Zhejiang University, Hangzhou, People's Republic of China.
Oncologist. 2022 Aug 5;27(8):e625-e632. doi: 10.1093/oncolo/oyac097.
Neuroendocrine neoplasms (NENs) are a group of diseases that show high heterogeneity but have limited treatment options. This phase I study evaluated the safety and efficacy of sintilimab, anti-PD-1 monoclonal antibody, in treating advanced NENs.
We prospectively enrolled patients pathologically diagnosed with NENs after standard treatment failure. Neuroendocrine neoplasms were classified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine cancers (NECs). Every patient received sintilimab, and response was assessed every 9 weeks.
Twenty-four patients with a median age of 57.0 years were enrolled from November 2016 to 2017. The median Ki-67 index was 60%. Five patients had NET, 1 had NET G3, 17 had NEC, and 1 had mixed adenocarcinoma-neuroendocrine carcinoma. The most common primary tumor sites were the pancreas and gastrointestinal tract in 7 and 10 patients, respectively. In phase Ia trial, 2 patients received sintilimab 1 mg/kg every 2 weeks, one received 3 mg/kg every 2 weeks, and 21 patients enrolled in the phase Ib trial received 200 mg every 3 weeks. The objective response rate was 20.8% in all enrolled patients and 27.8% in NEC patients. The median progression-free survival was 2.2 and 2.1 months in patients with NET and NEC, respectively. The median OS was not applicable (NA) and 10.8 months (95% CI, 4.3, NA) with NET and NEC, respectively. The duration of response (DOR) was not reached, with a median follow-up time of 20.7 months. Treatment-related adverse events (TRAE) occurred in 17 (70.8%) patients. The most frequent TRAE was thyroid dysfunction (41.7%), and a grade 3 pulmonary infection occurred in 1 patient. The programmed cell death 1-ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) rate was 18.8% (3 out of 16) and the expression of PD-L1 did not correlate with response.
Sintilimab was well-tolerated and showed encouraging response in NECs.
CLINICALTRIALS.GOV IDENTIFIER: NCT02937116.
神经内分泌肿瘤（NENs）是一组表现出高度异质性但治疗选择有限的疾病。这项 I 期研究评估了抗 PD-1 单克隆抗体信迪利单抗治疗晚期 NENs 的安全性和疗效。
我们前瞻性地招募了在标准治疗失败后经病理诊断为 NENs 的患者。神经内分泌肿瘤分为分化良好的神经内分泌肿瘤（NETs）和分化差的神经内分泌癌（NECs）。每位患者均接受信迪利单抗治疗，每 9 周评估一次应答。
2016 年 11 月至 2017 年共纳入 24 例中位年龄为 57.0 岁的患者。中位 Ki-67 指数为 60%。5 例为 NET，1 例为 NET G3，17 例为 NEC，1 例为混合性腺癌-神经内分泌癌。最常见的原发肿瘤部位分别为胰腺和胃肠道，分别为 7 例和 10 例。在 Ia 期试验中，2 例患者接受信迪利单抗 1 mg/kg，每 2 周 1 次；1 例患者接受信迪利单抗 3 mg/kg，每 2 周 1 次；21 例患者进入 Ib 期试验，接受信迪利单抗 200 mg，每 3 周 1 次。所有入组患者的客观缓解率为 20.8%，NEC 患者的客观缓解率为 27.8%。NET 和 NEC 患者的中位无进展生存期分别为 2.2 个月和 2.1 个月。NET 和 NEC 患者的中位总生存期均未达到，分别为 10.8 个月（95%CI，4.3，未达到）和 10.8 个月（95%CI，4.3，未达到）。缓解持续时间（DOR）未达到，中位随访时间为 20.7 个月。17 例（70.8%）患者发生治疗相关不良事件（TRAE）。最常见的 TRAE 是甲状腺功能障碍（41.7%），1 例患者发生 3 级肺部感染。程序性死亡配体 1（PD-L1）阳性（肿瘤比例评分≥1%）率为 18.8%（3/16），PD-L1 的表达与应答无关。
信迪利单抗在 NECs 中具有良好的耐受性和令人鼓舞的应答。
临床试验.gov 标识符：NCT02937116。
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