Stereotactic body radiotherapy with sequential tislelizumab and chemotherapy as neoadjuvant therapy in patients with resectable non-small-cell lung cancer in China (SACTION01): a single-arm, single-centre, phase 2 trial.

IF 38.7 1区医学 Q1 CRITICAL CARE MEDICINE Lancet Respiratory Medicine Pub Date : 2024-09-18 DOI:10.1016/S2213-2600(24)00215-7

Ze-Rui Zhao, Shi-Liang Liu, Ting Zhou, Gang Chen, Hao Long, Xiao-Dong Su, Xu Zhang, Jian-Hua Fu, Peng Lin, Lan-Jun Zhang, Tie-Hua Rong, Jia-Di Wu, Zhi-Chao Li, Hui-Lin Su, Ji-Yang Chen, Yun-Peng Yang, Yong-Bin Lin, Mian Xi, Hong Yang

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Abstract

Background: Neoadjuvant immunotherapy with chemotherapy improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Given its immunomodulating effect, we investigated whether stereotactic body radiotherapy (SBRT) enhances the effect of immunochemotherapy.

Methods: The SACTION01 study was a single-arm, open-label, phase 2 trial that recruited patients who were 18 years or older and had resectable stage IIA-IIIB NSCLC from the Sun Yat-sen University Cancer Center, Guangzhou, China. Eligible patients received SBRT (24 Gy in three fractions) to the primary tumour followed by two cycles of 200 mg intravenous PD-1 inhibitor, tislelizumab, plus platinum-based chemotherapy. Surgical resection was performed 4-6 weeks after neoadjuvant treatment. The primary endpoint was major pathological response (MPR), defined as no more than 10% residual viable tumour in the resected tumour. All analyses were conducted on an intention-to-treat basis, including all patients who were scheduled for neoadjuvant treatment. The trial was registered with ClinicalTrials.gov (NCT05319574) and is ongoing but closed to recruitment.

Findings: Between May 18, 2022, and June 20, 2023, 46 patients (42 men and four women) were enrolled and scheduled for neoadjuvant treatment. MPR was observed in 35 (76%, 95% CI 61-87) of 46 patients. The second cycle of immunochemotherapy was withheld in four (9%) patients due to pneumonia (n=2), colitis (n=1), and increased creatinine (n=1). Grade 3 or worse adverse events related to neoadjuvant treatment occurred in 12 (26%, 95% CI 14-41) patients. The most frequent treatment-related adverse event (TRAE) was alopecia (16 [35%] patients), and the most frequent grade 3 or worse TRAE was neutropenia (six [13%]). There was one treatment-related death, caused by neutropenia. No deaths within 90 days of surgery were reported.

Interpretation: Preoperative SBRT followed by immunochemotherapy is well tolerated, feasible, and leads to a clinically significant MPR rate. Future randomised trials are warranted to support these findings.

Funding: BeiGene.

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中国可切除非小细胞肺癌患者的立体定向体放疗联合替赛珠单抗和化疗新辅助治疗（SACTION01）：单臂、单中心、2 期试验。

背景：新辅助免疫治疗与化疗可改善可切除非小细胞肺癌（NSCLC）患者的预后。鉴于其免疫调节作用，我们研究了立体定向体放射治疗（SBRT）是否能增强免疫化疗的效果：SACTION01研究是一项单臂、开放标签的2期试验，招募了中国广州中山大学肿瘤防治中心18岁或18岁以上可切除的IIA-IIIB期NSCLC患者。符合条件的患者先接受SBRT（24 Gy，分三次）治疗原发肿瘤，然后接受两个周期的200 mg静脉注射PD-1抑制剂tislelizumab和铂类化疗。手术切除在新辅助治疗后4-6周进行。主要终点是主要病理反应（MPR），即切除肿瘤中残留的有活力肿瘤不超过10%。所有分析均在意向治疗基础上进行，包括所有计划接受新辅助治疗的患者。该试验已在ClinicalTrials.gov（NCT05319574）上注册，目前正在进行中，但已结束招募：2022年5月18日至2023年6月20日期间，46名患者（42名男性和4名女性）登记并计划接受新辅助治疗。46 名患者中有 35 人（76%，95% CI 61-87）观察到 MPR。由于肺炎（2例）、结肠炎（1例）和肌酐升高（1例），有4例（9%）患者暂停了第二周期免疫化疗。12例（26%，95% CI 14-41）患者发生了与新辅助治疗相关的3级或更严重不良事件。最常见的治疗相关不良事件（TRAE）是脱发（16 [35%]名患者），最常见的3级或更严重的TRAE是中性粒细胞减少（6 [13%]名患者）。有一例与治疗相关的死亡病例是由中性粒细胞减少症引起的。术后90天内无死亡报告：术前SBRT术后免疫化疗的耐受性良好、可行，并能带来显著的MPR率。未来有必要进行随机试验来支持这些研究结果：资金来源：BeiGene.

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来源期刊

Lancet Respiratory Medicine RESPIRATORY SYSTEM-RESPIRATORY SYSTEM

CiteScore

87.10

自引率

0.70%

发文量

572

期刊介绍： The Lancet Respiratory Medicine is a renowned journal specializing in respiratory medicine and critical care. Our publication features original research that aims to advocate for change or shed light on clinical practices in the field. Additionally, we provide informative reviews on various topics related to respiratory medicine and critical care, ensuring a comprehensive coverage of the subject. The journal covers a wide range of topics including but not limited to asthma, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), tobacco control, intensive care medicine, lung cancer, cystic fibrosis, pneumonia, sarcoidosis, sepsis, mesothelioma, sleep medicine, thoracic and reconstructive surgery, tuberculosis, palliative medicine, influenza, pulmonary hypertension, pulmonary vascular disease, and respiratory infections. By encompassing such a broad spectrum of subjects, we strive to address the diverse needs and interests of our readership.