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Supplementary Data 1 from Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naïve Stage IV PD-L1+ Non–Small Cell Lung Cancer Patients

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posted on 2023-10-13, 07:41 authored by Xiaojuan Zhou, Laiyan Zhou, Zhuoran Yao, Meijuan Huang, Youling Gong, Bingwen Zou, Jiang Zhu, Yongmei Liu, Feng Peng, Yan Zhang, Min Yu, Yanying Li, Feifei Na, Yijun Wu, Kai Kang, Weigang Xiu, Xuanwei Zhang, Lin Zhou, Yong Xu, Jin Wang, Yan Wang, Xue Yang, Yuanjun Wu, Rui Li, Yu Zhang, Zhenzhou Yang, Zhipeng Zhou, Jing Bai, Xin Yi, Ruizhan Tong, Limei Yin, Chong Chen, Gabriele Niedermann, You Lu, Jianxin Xue

2 figures,3 tables and 3 texts

Funding

West China Hospital, Sichuan University (WCH)

National Natural Science Foundation of China

Bethune Cancer Radiotherapy Translational Medicine Research Foundation

Sichuan Cancer Society Foundation

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ARTICLE ABSTRACT

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). 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). 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. 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.

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