西妥昔单抗、立体定向体部放疗和粒细胞-巨噬细胞集落刺激因子作为二线治疗晚期非小细胞肺癌的研究：一项多中心、单臂、Ⅱ期试验的安全性预试验结果。
Sintilimab, stereotactic body radiotherapy and granulocyte-macrophage colony stimulating factor as second-line therapy for advanced non-small cell lung cancer: safety run-in results of a multicenter, single-arm, phase II trial.
机构信息
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
出版信息
Radiat Oncol. 2021 Sep 15;16(1):177. doi: 10.1186/s13014-021-01905-3.
OBJECTIVES
The SWORD trial is the first multicenter, single arm, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), stereotactic body radiotherapy (SBRT) and granulocyte-macrophage colony stimulating factor (GM-CSF) in advanced non-small cell lung cancer (NSCLC) without sensitizing driver mutations. A safety run-in phase was conducted to determine the tolerability of the experimental treatment.
MATERIALS AND METHODS
Twenty metastatic NSCLC patients who failed first-line chemotherapy were enrolled, and they received SBRT (8 Gy × 3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks, until disease progression, unacceptable toxicity, or up to 35 cycles) and GM-CSF (125 μg/m d1-d14, cycle 1) within 2 weeks after SBRT. In addition, blood and tissue samples were serially collected for translational research.
RESULTS
Median age of the patients was 61 and all of them had more than 5 lesions at baseline. The sites of SBRT included lung (n = 11), mediastinal lymph node (n = 5), liver (n = 1), abdominal lymph node (n = 1), pleural nodule (n = 1) and vertebra (n = 1). No patients had dose-limiting toxicities (DLTs) and 18 patients experienced treatment-related adverse event (TRAE). The most common TRAEs were fatigue (50%), fever (30%), and ostealgia (20%), and they all were grade 1. Only 2 grade 3 TRAEs were observed, including elevation of liver enzymes in one and transient acute heart failure in another. No grade 4 or 5 AE was observed.
CONCLUSION
Sintilimab, SBRT and GM-CSF for advanced NSCLC is safe with manageable TRAEs and the trial continues to recruit participants. Trial registration ClinicalTrials.gov, NCT04106180. Registered 26 September 2019, SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC-Tabular View-ClinicalTrials.gov.
目的
SWORD 试验是第一项评估 PD-1 抑制剂（信迪利单抗）、立体定向体部放疗（SBRT）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）联合治疗无致敏驱动突变的晚期非小细胞肺癌（NSCLC）的安全性和有效性的多中心、单臂、二期研究。进行了一个安全入组阶段，以确定实验治疗的耐受性。
材料和方法
共纳入 20 例一线化疗失败的转移性 NSCLC 患者，他们接受了 SBRT（8Gy×3）治疗一个病灶，随后在 SBRT 后 2 周内接受信迪利单抗（200mg d1，每 3 周一次，直到疾病进展、不可接受的毒性或最多 35 个周期）和 GM-CSF（125μg/m d1-d14，周期 1）。此外，还连续采集血液和组织样本进行转化研究。
结果
患者的中位年龄为 61 岁，所有患者基线时均有超过 5 个病灶。SBRT 的部位包括肺（n=11）、纵隔淋巴结（n=5）、肝（n=1）、腹部淋巴结（n=1）、胸膜结节（n=1）和椎体（n=1）。无患者发生剂量限制性毒性（DLTs），18 例患者发生治疗相关不良事件（TRAE）。最常见的 TRAE 是疲劳（50%）、发热（30%）和骨痛（20%），均为 1 级。仅观察到 2 例 3 级 TRAE，包括 1 例肝酶升高和 1 例短暂性急性心力衰竭。未观察到 4 或 5 级 AE。
结论
信迪利单抗、SBRT 和 GM-CSF 联合治疗晚期 NSCLC 是安全的，具有可管理的 TRAE，试验仍在招募参与者。试验注册ClinicalTrials.gov，NCT04106180。于 2019 年 9 月 26 日注册，SBRT 联合信迪利单抗和 GM-CSF 治疗晚期 NSCLC 的临床试验-表格视图-ClinicalTrials.gov。
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