安全性和耐受性评估：治疗初始期IV期PD-L1阳性非小细胞肺癌患者的低剂量放射和体部立体定向放疗 + 信迪利单抗

SCI

30 August 2023

Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naive Stage IV PD-L1+ Non- Small-Cell Lung Cancer Patients

（Clinical cancer research；IF：11.5）

Zhou X, Zhou L, Yao Z, Huang M, Gong Y, Zou B, Zhu J, Liu Y, Peng F, Zhang Y, Yu M, Li Y, Na F, Wu Y, Kang K, Xiu W, Zhang X, Zhou L, Xu Y, Wang J, Wang Y, Yang X, Wu Y, Li R, Zhang Y, Yang Z, Zhou Z, Bai J, Yi X, Tong R, Yin L, Chen C, Niedermann G, Lu Y, Xue J. Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naive Stage IV PD-L1+ Non-Small-Cell Lung Cancer Patients. Clin Cancer Res. 2023 Aug 15:CCR-23-0315. doi: 10.1158/1078-0432.CCR-23-0315. Epub ahead of print. PMID: 37581611.

Corresponding authors: You Lu ，Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China，Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China ，Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China ，Phone: +86-18980601763，Email: radyoulu@hotmail.com &Jianxin Xue Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China，Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDisaster Medical Center, Sichuan University, Chengdu, Sichuan, China，Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China ，Phone: +86-18982251798 ，Email: radjianxin@163.com

PURPOSE 目的

Low-dose radiation therapy (LDRT) may enhance the synergistic anti-tumor effect of combined immunotherapy and stereotactic body radiation therapy (SBRT). The safety and efficacy of this novel triple-combination therapy were evaluated for the first time as first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC).

低剂量放射治疗（LDRT）可能增强联合免疫治疗和体部立体定向放疗（SBRT）的协同抗肿瘤效果。首次评估了这种新的三联疗法作为转移性非小细胞肺癌（NSCLC）患者一线治疗的安全性和有效性。

METHODS 方法

This prospective phase 1 study enrolled 29 patients and included a dose-escalation and dose-expansion phase. Patients received SBRT (30 Gy/3f) to small lesions and LDRT (2 Gy/1f, 4 Gy/2f, or 10 Gy/5f) to a large lesion concurrently, followed by sintilimab (a PD-1 inhibitor). The primary endpoint was safety and tolerability; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). 

本前瞻性1期研究共招募了29名患者，包括剂量递增和剂量扩展阶段。患者同时接受SBRT（30 Gy/3f）针对小病变和LDRT（2 Gy/1f, 4 Gy/2f, 或 10 Gy/5f）针对大病变，然后接受信迪利单抗（PD-1抑制剂）。主要终点是安全性和耐受性；次要终点包括客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。

RESULTS 结果

No dose-limiting toxicities were observed during the dose-escalation phase; 4 Gy/2f was the recommended LDRT dose. Median follow-up was 15.6 months. Treatment-related adverse events (TRAEs) occurred in 96.6% (28/29) of patients (grade ≥ 3, 20.7% [6/29]); two patients (6.9%) discontinued due to TRAEs. Seven patients experienced pneumonitis (grade 2, n = 6; grade 3, n = 1). Immune-related adverse events were noted in 58.6% (17/29) of patients. In patients with tumor assessment (n = 28), ORR and confirmed ORR were 60.7% and 57.1%, respectively. Median PFS was 8.6 months (95% confidence interval 3.7–16.5), and median OS was not reached. Exploratory analyses suggested both expanded and newly emerging TCR clonotypes were associated with better PFS. 

在剂量递增阶段未观察到剂量限制性毒性；推荐的LDRT剂量为4 Gy/2f。中位随访时间为15.6个月。治疗相关不良事件（TRAEs）发生在96.6%（28/29）的患者中（3级或以上，20.7% [6/29]）；两名患者（6.9%）因TRAEs中止治疗。七名患者出现肺炎（2级，n = 6；3级，n = 1）。免疫相关不良事件出现在58.6%（17/29）的患者中。在进行肿瘤评估的患者（n = 28）中，ORR和确认的ORR分别为60.7%和57.1%。中位PFS为8.6个月（95%置信区间3.7-16.5），中位OS尚未到达。探索性分析表明，扩张的和新出现的TCR克隆型与更好的PFS相关。

CONCLUSIONS 结论

The findings indicate that the novel SBRT + LDRT + sintilimab therapy is safe and promising in patients with PD-L1-positive, driver gene-negative primary metastatic NSCLC.

研究发现，新的SBRT + LDRT + 信迪利单抗治疗对于PD-L1阳性，驱动基因阴性的原发性转移性NSCLC患者是安全且有前景的。

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