{"title":"食管鳞状细胞癌托利帕利单抗加确定性化放疗的长期生存期和事后分析：EC-CRT-001 II 期试验的启示。","authors":"Ruixi Wang, Yihong Ling, Baoqing Chen, Yujia Zhu, Yonghong Hu, Mengzhong Liu, Yadi Yang, Li Zhang, Yingxin Lv, Shiliang Liu, Qiaoqiao Li, Mian Xi","doi":"10.1016/j.eclinm.2024.102806","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses.</p><p><strong>Methods: </strong>This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m<sup>2</sup> of paclitaxel and 25 mg/m<sup>2</sup> of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170).</p><p><strong>Findings: </strong>With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, <i>P <</i> 0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, <i>P <</i> 0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, <i>P</i> = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, <i>P</i> = 0.027) than those without irAEs. <i>GON4L</i> mutation was associated with a lower incidence of irAEs (<i>P</i> = 0.036).</p><p><strong>Interpretation: </strong>The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis.</p><p><strong>Funding: </strong>National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":null,"pages":null},"PeriodicalIF":9.6000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402426/pdf/","citationCount":"0","resultStr":"{\"title\":\"Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial.\",\"authors\":\"Ruixi Wang, Yihong Ling, Baoqing Chen, Yujia Zhu, Yonghong Hu, Mengzhong Liu, Yadi Yang, Li Zhang, Yingxin Lv, Shiliang Liu, Qiaoqiao Li, Mian Xi\",\"doi\":\"10.1016/j.eclinm.2024.102806\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). 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引用次数: 0
摘要
研究背景在EC-CRT-001 II期研究中，托瑞帕利单抗（一种抗程序性死亡-1抗体）与确定性化放疗（CRT）联合治疗局部晚期食管鳞状细胞癌（ESCC）患者显示出良好的疗效。在此，我们报告了长期疗效和事后探索性分析：这项单臂 II 期试验于 2019 年 11 月至 2021 年 1 月在中山大学肿瘤防治中心进行，共招募了 42 例诊断为不可切除的 I-IVA 期 ESCC 患者。治疗包括化疗（每周50 mg/m2紫杉醇和25 mg/m2顺铂，共5个周期）、同步放疗（50.4 Gy，28次分割）和托利帕单抗（240 mg，每3周一次，最长1年）。主要终点是CRT结束后3个月的临床完全应答率（CR）。同时还评估了3年总生存率（OS）和无进展生存率（PFS）。此外，探索性目标还包括分析复发模式、评估免疫相关不良事件（irAEs）与疗效之间的关联以及确定irAEs的潜在预测因素。该试验已在ClinicalTrials.gov（NCT04005170）上注册：中位随访时间为44.3个月（IQR 40.8-46.1），3年OS和PFS率分别为44.8%（95% CI 31.9-62.8）和35.7%（95% CI 23.8-53.6）。未能获得临床完全应答（CR）的患者的OS（危险比[HR] = 13.73，95% CI 4.43-42.54，P 0.0001）和PFS（HR = 32.08，95% CI 8.57-120.10，P 0.0001）明显降低。42例患者中有23例（55%）出现疾病复发，与CR组相比，非CR组复发更早、更频繁。与无irAEs的患者相比，有irAEs的患者的CR率明显更高（72% vs. 39%，P = 0.082），PFS也更好（HR = 0.43，95% CI 0.19-0.93，P = 0.027）。GON4L突变与较低的虹膜AEs发生率相关（P = 0.036）：最新的生存结果证实了托利帕利单抗联合最终CRT治疗局部晚期ESCC的疗效。此外，irAEs的发生可能预示着更有利的预后：国家自然科学基金、北京希赛克临床肿瘤学研究基金、广州市科技项目基金。
Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial.
Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses.
Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170).
Findings: With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, P < 0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, P < 0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, P = 0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P = 0.036).
Interpretation: The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis.
Funding: National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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