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

Clin Cancer Res. 2023 Oct 13;29(20):4098-4108. doi: 10.1158/1078-0432.CCR-23-0315.

Authors

Xiaojuan Zhou^#^{1

2}, Laiyan Zhou^#^{1

3}, Zhuoran Yao^#^{1

4}, Meijuan Huang¹, Youling Gong^{1

2}, Bingwen Zou^{1

2}, Jiang Zhu¹, Yongmei Liu^{1

2}, Feng Peng¹, Yan Zhang¹, Min Yu¹, Yanying Li¹, Feifei Na¹, Yijun Wu^{1

4}, Kai Kang^{1

4}, Weigang Xiu¹, Xuanwei Zhang¹, Lin Zhou^{1

2}, Yong Xu^{1

2}, Jin Wang^{1

2}, Yan Wang¹, Xue Yang¹, Yuanjun Wu¹, Rui Li⁵, Yu Zhang⁶, Zhenzhou Yang⁷, Zhipeng Zhou⁸, Jing Bai⁸, Xin Yi⁸, Ruizhan Tong^{1

4}, Limei Yin¹, Chong Chen⁹, Gabriele Niedermann¹⁰, You Lu^{1

2

4}, Jianxin Xue^{1

2

3

4}

Affiliations

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.
⁵ Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, China.
⁶ Department of Oncology, 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.
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.

^# Contributed equally.

PMID: 37581611
DOI: 10.1158/1078-0432.CCR-23-0315

Abstract

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.

Abstract

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