Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial

Journal of Translational Medicine

Research

Yuanheng Huang¹  Qiyu Guo¹  Xu Zhang¹  Jiudi Zhong¹  Guozhen Yang¹  Xiaodong Su¹  Yuezong Bai²  Ting Bei²  Yating Zheng²  Mengli Huang²  Guangyu Luo³  Peiqiang Cai⁴  Haoqiang He⁴  Zhiqiang Wang⁵  Muyan Cai⁶  Jin Xiang⁶ 

[1] Department of Thoracic Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China;Guangdong Esophageal Cancer Institute, Guangzhou, China;State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China;Medical Affairs, 3D Medicines, Inc, Shanghai, China;State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China;Department of Endoscopy, Sun Yat-Sen University Cancer Center, Guangzhou, China;State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China;Department of Medical Imaging and Interventional Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, China;State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China;Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China;State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China;Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China;

关键词: Neoadjuvant;    Immunotherapy;    Chemotherapy;    ESCC;   

DOI  :  10.1186/s12967-023-04273-6

 received in 2023-03-15, accepted in 2023-06-13,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTwo cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indicating that a short course of treatment may not be sufficient. Therefore, exploring the effects of intensive treatment is needed for optimal clinical outcomes.MethodsLocally advanced ESCC patients were administered three cycles of camrelizumab plus nab-paclitaxel and capecitabine, followed by thoracoscopic esophagectomy. The primary endpoint was pathologic response. Secondary endpoints included safety, feasibility, radiologic response, survival outcomes, and immunologic/genomic correlates of efficacy.ResultsForty-seven patients were enrolled in the study. Forty-two patients received surgery, and R0 resection was achieved in all cases. The complete and major pathological response rates were 33.3% and 64.3%, respectively, and the objective response rate was 80.0%. Three cycles of treatment significantly improved T down-staging compared to two cycles (P = 0.03). The most common treatment-related adverse events were grades 1–2, and no surgical delay was reported. With a median follow-up of 24.3 months, the 1-year disease-free survival and overall survival rates were both 97.6%, and the 2-year disease-free survival and overall survival rates were 92.3% and 97.6%, respectively. Three patients experienced disease recurrence or metastasis ranging from 12.5 to 25.8 months after surgery, and one patient died 6 months after surgery due to cardiovascular disease. Neither programmed death-ligand 1 expression nor tumor mutational burden was associated with pathological response. An increased infiltration of CD56dim natural killer cells in the pretreatment tumor was correlated with better pathological response in the primary tumor.ConclusionsIt seems probable that intensive cycles of neoadjuvant camrelizumab plus nab-paclitaxel and capecitabine increased tumor regression and improved survival outcomes. Randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings.Trial registration Chinese Clinical Trial Registry, ChiCTR2000029807, Registered February 14, 2020, https://www.chictr.org.cn/showproj.aspx?proj=49459.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 2

13690_2023_1130_Article_IEq53.gif

Fig. 2