DOI: 10.1158/1078-0432.ccr-23-0315 ISSN:

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

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
  • Cancer Research
  • Oncology


Purpose: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). Patients and Methods: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). 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 (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. Conclusions: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.

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