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

作者全名："Zhou, Xiaojuan; Zhou, Laiyan; Yao, Zhuoran; Huang, Meijuan; Gong, Youling; Zou, Bingwen; Zhu, Jiang; Liu, Yongmei; Peng, Feng; Zhang, Yan; Yu, Min; Li, Yanying; Na, Feifei; Wu, Yijun; Kang, Kai; Xiu, Weigang; Zhang, Xuanwei; Zhou, Lin; Xu, Yong; Wang, Jin; Wang, Yan; Yang, Xue; Wu, Yuanjun; Li, Rui; Zhang, Yu; Yang, Zhenzhou; Zhou, Zhipeng; Bai, Jing; Yi, Xin; Tong, Ruizhan; Yin, Limei; Chen, Chong; Niedermann, Gabriele; Lu, You; Xue, Jianxin"

作者地址："[Zhou, Xiaojuan; Zhou, Laiyan; Yao, Zhuoran; Huang, Meijuan; Gong, Youling; Zou, Bingwen; Zhu, Jiang; Liu, Yongmei; Peng, Feng; Zhang, Yan; Yu, Min; Li, Yanying; Na, Feifei; Wu, Yijun; Kang, Kai; Xiu, Weigang; Zhang, Xuanwei; Zhou, Lin; Xu, Yong; Wang, Jin; Wang, Yan; Yang, Xue; Wu, Yuanjun; Tong, Ruizhan; Yin, Limei; Lu, You; Xue, Jianxin] Sichuan Univ, West China Hosp, Div Thorac Tumor Multimodal Treatment, Ctr Canc, Chengdu, Sichuan, Peoples R China; [Zhou, Xiaojuan; Gong, Youling; Zou, Bingwen; Liu, Yongmei; Zhou, Lin; Xu, Yong; Wang, Jin; Lu, You; Xue, Jianxin] Sichuan Univ, West China Hosp, Dept Radiat Oncol, Ctr Canc, Chengdu, Sichuan, Peoples R China; [Zhou, Laiyan; Xue, Jianxin] Sichuan Univ, Disaster Med Ctr, Chengdu, Sichuan, Peoples R China; [Yao, Zhuoran; Wu, Yijun; Kang, Kai; Tong, Ruizhan; Lu, You; Xue, Jianxin] Sichuan Univ, West China Hosp, Lab Clin Cell Therapy, Chengdu, Sichuan, Peoples R China; [Li, Rui] Sichuan Univ, Dept Obstet & Gynecol, West China Univ Hosp 2, Chengdu, Peoples R China; [Zhang, Yu] Guizhou Prov Peoples Hosp, Dept Oncol, Guiyang, Peoples R China; [Yang, Zhenzhou] Chongqing Med Univ, Ctr Canc, Affiliated Hosp 2, Chongqing, Peoples R China; [Zhou, Zhipeng; Bai, Jing; Yi, Xin] Geneplus Beijing Inst, Beijing, Peoples R China; [Chen, Chong] Sichuan Univ, West China Hosp, State Key Lab Biotherapy & Canc Ctr, Chengdu, Peoples R China; [Niedermann, Gabriele] Univ Freiburg, Dept Radiat Oncol, Fac Med, Freiburg, Germany; [Niedermann, Gabriele] German Canc Consortium DKTK, Partner Site Freiburg, Heidelberg, Germany; [Niedermann, Gabriele] German Canc Res Ctr, Heidelberg, Germany"

通信作者："Lu, Y; Xue, JX (通讯作者)，Sichuan Univ, West China Hosp, Div Thorac Tumor Multimodal Treatment, Ctr Canc, Chengdu, Sichuan, Peoples R China.; Xue, JX (通讯作者)，Sichuan Univ, West China Hosp, Dept Radiat Oncol, Ctr Canc, Chengdu, Sichuan, Peoples R China.; Xue, JX (通讯作者)，Sichuan Univ, Disaster Med Ctr, Chengdu, Sichuan, Peoples R China.; Xue, JX (通讯作者)，Sichuan Univ, West China Hosp, Lab Clin Cell Therapy, Chengdu, Sichuan, Peoples R China."

来源：CLINICAL CANCER RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001189711100012

JCR分区：Q1

影响因子：11.5

年份：2023

卷号：29

期号：20

开始页：4098

结束页：4108

文献类型：Article

关键词：　

摘要："Purpose: Low-dose radiotherapy (LDRT) may enhance the synergistic antitumor effect of combined immunotherapy and stereotactic body radiotherapy (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). Patients and Methods: This prospective phase I study enrolled 29 patients and included a dose-escalation and dose-expansion phase. Patients received SBRT [30 Gray (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 programmed death-1 inhibitor). The primary endpoint was safety and tolerability; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 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 (TRAE) occurred in 96.6% (28/29) of patients [grade >= 3; 20.7% (6/29)]; 2 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 T-cell receptor clonotypes were associated with better PFS. Conclusions: The findings indicate that the novel SBRT + LDRT + sintilimab therapy is safe and promising in patients with programmed death ligand-1-positive, driver gene-negative primary metastatic NSCLC."

基金机构："1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZYJC21003, 2021HXFH023]; National Natural Science Foundation of China [82073336, 81872478]; Cancer Radiotherapy Translational Medicine Research Foundation [flzh202110]; Sichuan Cancer Society Foundation [SCS-KT002]; Bethune"

基金资助正文："This work was supported by grants from the 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).; The authors thank Li Li, Qi Lu, and Jinrong Du of the GCP team for the trial support and the nursing team for providing clinical care. We thank all participating patients and their family members. We thank Dr. YuquanWei for his administrative assistance. We also thank Sarah Bubeck, PhD, of Edanz (www.edanz.com) for providing medical writing support, in accordance with Good Publication Practice (GPP) 2022 guidelines (https://www.ismpp.org/gpp-2022).; The publication costs of this article were defrayed in part by the payment of publication fees. Therefore, and solely to indicate this fact, this article is hereby marked ""advertisement"" in accordance with 18 USC section 1734."