在中国可切除非小细胞肺癌患者中序贯替雷利珠单抗与化疗作为新辅助治疗的立体定向体部放射治疗（SACTION01）：一项单臂、单中心的2期试验。
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.
作者信息
Zhao Ze-Rui, Liu Shi-Liang, Zhou Ting, Chen Gang, Long Hao, Su Xiao-Dong, Zhang Xu, Fu Jian-Hua, Lin Peng, Zhang Lan-Jun, Rong Tie-Hua, Wu Jia-Di, Li Zhi-Chao, Su Hui-Lin, Chen Ji-Yang, Yang Yun-Peng, Lin Yong-Bin, Xi Mian, Yang Hong
机构信息
Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
出版信息
Lancet Respir Med. 2024 Dec;12(12):988-996. doi: 10.1016/S2213-2600(24)00215-7. Epub 2024 Sep 18.
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.
背景
新辅助免疫治疗联合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部放疗（SBRT）是否能增强免疫化疗的效果。
方法
SACTION01研究是一项单臂、开放标签的2期试验，招募了来自中国广州中山大学肿瘤防治中心的18岁及以上、患有可切除的IIA-IIIB期NSCLC的患者。符合条件的患者接受对原发肿瘤的SBRT（分3次给予24 Gy），随后进行两个周期的200 mg静脉注射PD-1抑制剂替雷利珠单抗加铂类化疗。新辅助治疗4-6周后进行手术切除。主要终点是主要病理缓解（MPR），定义为切除肿瘤中残留存活肿瘤不超过10%。所有分析均基于意向性分析，包括所有计划接受新辅助治疗的患者。该试验已在ClinicalTrials.gov注册（NCT05319574），正在进行但已停止招募。
结果
在2022年5月18日至2023年6月20日期间，46例患者（42例男性和4例女性）入组并计划接受新辅助治疗。46例患者中有35例（76%，95%CI 61-87）观察到MPR。4例（9%）患者因肺炎（2例）、结肠炎（1例）和肌酐升高（1例）而停用免疫化疗的第二个周期。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例[35%]患者），最常见的3级或更严重TRAE是中性粒细胞减少（6例[13%]）。有1例与治疗相关的死亡，由中性粒细胞减少引起。未报告术后90天内死亡。
解读
术前SBRT联合免疫化疗耐受性良好、可行，并导致具有临床意义的MPR率。未来需要进行随机试验以支持这些发现。
资助
百济神州。
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