Ding Chengzhi, Zhang Yahao, Xia Tian, Li Jiwei, Yao Wenjian, Zhang Quan, Han Zhijun, Wang Jianjun, Cao Zhikun, Hu Jinlong, Wei Li
Department of Thoracic Surgery, Henan Provincial People's Hospital; Zhengzhou University People's Hospital, Zhengzhou, China.
Department of Oncology, Henan Provincial People's Hospital; Zhengzhou University People's Hospital, Zhengzhou, China.
Front Immunol. 2025 Apr 10;16:1542877. doi: 10.3389/fimmu.2025.1542877. eCollection 2025.
The treatment of cancer has brought about a paradigm shift with the introduction of immune checkpoint blockade (ICB) therapy, which is mostly dependent on inhibiting PD-1/PD-L1 and CTLA-4. However, recent studies have shown limited efficacy of this treatment in esophageal squamous cell carcinoma (ESCC). Preliminary studies have found that tifcemalimab (the world's first anti-BTLA blocking monoclonal antibody) combined with toripalimab (PD-1) and chemotherapy has shown favorable safety and efficacy in several solid cancers. This study aimed to evaluate the safety and efficacy of neoadjuvant tifcemalimab combined with toripalimab and chemotherapy following esophagectomy for resectable ESCC, and the association of adjuvant immunotherapy with improved survival outcomes.
Patients with pathologically confirmed cT1b-3N1-3M0 or cT2-3N0M0 thoracic ESCC were treated with neoadjuvant tifcemalimab (200mg, iv, d1) in combination with toripalimab (240mg, iv, d1) and chemotherapy (paclitaxel 135-175 mg/m, d1 + cisplatin 75 mg/m, d1) every 3 weeks for 2 cycles. Patients undergoing esophagectomy with pathological complete response (pCR) were administered up to 15 cycles of adjuvant tifcemalimab (200 mg) and toripalimab (240 mg), whereas patients without pCR received tifcemalimab in combination with toripalimab and adjuvant chemotherapy for 2 cycles, followed by tifcemalimab in combination with toripalimab immunotherapy up to 13 cycles. The patient with incomplete resection was decided to receive radiotherapy after a multidisciplinary consultation. The primary endpoint of this study was the pCR rate. The secondary endpoints include major pathological response rate (MPR), objective response rate (ORR), disease control rate (DCR), adverse events, R0 resection rate, event-free survival (EFS), and overall survival (OS).
The Ethics Committee of Henan Provincial People's Hospital has approved the protocol (No 2024-132-03). This study is the world's first prospective clinical trial to evaluate the safety and efficacy of the BTLA inhibitor in combination with PD-1 and chemotherapy as neoadjuvant/adjuvant therapy for locally advanced thoracic ESCC. We predicted that perioperative combination immunotherapy as a potentially preferred and effective treatment strategy may lead to better survival outcomes.
免疫检查点阻断（ICB）疗法的引入使癌症治疗发生了范式转变，该疗法主要依赖于抑制PD-1/PD-L1和CTLA-4。然而，最近的研究表明这种治疗在食管鳞状细胞癌（ESCC）中的疗效有限。初步研究发现，替西马利单抗（全球首个抗BTLA阻断单克隆抗体）联合托瑞帕利单抗（PD-1）及化疗在多种实体癌中显示出良好的安全性和疗效。本研究旨在评估新辅助替西马利单抗联合托瑞帕利单抗及化疗用于可切除ESCC食管切除术后的安全性和疗效，以及辅助免疫治疗与生存结局改善之间的关联。
经病理确诊为cT1b-3N1-3M0或cT2-3N0M0的胸段ESCC患者，接受新辅助替西马利单抗（200mg，静脉注射，第1天）联合托瑞帕利单抗（240mg，静脉注射，第1天）及化疗（紫杉醇135 - 175mg/m²，第1天 + 顺铂75mg/m²，第1天），每3周进行1次，共2个周期。接受食管切除术且达到病理完全缓解（pCR）的患者给予最多15个周期的辅助替西马利单抗（200mg）和托瑞帕利单抗（240mg），而未达到pCR的患者接受替西马利单抗联合托瑞帕利单抗及辅助化疗2个周期，随后接受替西马利单抗联合托瑞帕利单抗免疫治疗最多13个周期。切除不完全的患者经多学科会诊后决定接受放疗。本研究的主要终点是pCR率。次要终点包括主要病理缓解率（MPR）、客观缓解率（ORR）、疾病控制率（DCR）、不良事件、R0切除率、无事件生存期（EFS）和总生存期（OS）。
河南省人民医院伦理委员会已批准该方案（编号2024 - 132 - 03）。本研究是全球首个评估BTLA抑制剂联合PD-1及化疗作为局部晚期胸段ESCC新辅助/辅助治疗的安全性和疗效的前瞻性临床试验。我们预测围手术期联合免疫治疗作为一种潜在的首选有效治疗策略可能会带来更好的生存结局。
