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
机构：[1]Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China四川大学华西医院[2]Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China四川大学华西医院[3]Disaster Medical Center, Sichuan University, Chengdu, Sichuan, China[4]Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China四川大学华西医院[5]Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan, China[6]Department of Oncology, Guizhou Cancer Center, Guizhou Provincial People’s Hospital, Guiyang, China[7]Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China[8]Geneplus-Beijing Institute, Beijing, China[9]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China四川大学华西医院[10]Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany, German Cancer Consortium (DKTK), partner site Freiburg, and German Cancer Research Center, Heidelberg, Germany. Xiaojuan Zhou, Laiyan Zhou, and Zhuoran Yao contributed equally to the paper.
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).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).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.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.
基金：
1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYJC21003 and No.2021HXFH023); the National Natural Science Foundation of China (No.82073336 and No. 81872478); Bethune · Cancer Radiotherapy Translational Medicine Research Foundation (No. flzh202110); and the Sichuan Cancer Society Foundation (No. SCS-KT002).
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外文
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出版当年[2023]版：
大类|1 区医学
小类|1 区肿瘤学
最新[2023]版：
大类|1 区医学
小类|1 区肿瘤学
第一作者：
第一作者机构：[1]Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China[2]Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
共同第一作者：
通讯作者：
通讯机构：[1]Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China[2]Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China[3]Disaster Medical Center, Sichuan University, Chengdu, Sichuan, China[4]Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China[*1]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[*2]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.Disaster Medical Center, Sichuan University, Chengdu, Sichuan, China.Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University,Chengdu, Sichuan, China
推荐引用方式(GB/T 7714)：
Xiaojuan Zhou,Laiyan Zhou,Zhuoran Yao,et al.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[J].Clinical cancer research : an official journal of the American Association for Cancer Research.2023,doi:10.1158/1078-0432.CCR-23-0315.
APA：
Xiaojuan Zhou,Laiyan Zhou,Zhuoran Yao,Meijuan Huang,Youling Gong...&Jianxin Xue.(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 : an official journal of the American Association for Cancer Research,,
MLA：
Xiaojuan Zhou,et al."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 : an official journal of the American Association for Cancer Research .(2023)
医学