Shi Guoming, Huang Xiaoyong, Li Xiaowu, Liang Fei, Gao Qiang, Zhang Daohan, Lu Jiacheng, Ji Yuan, Hu Zhiqiang, Chen Yi, Qiu Shuangjian, Yi Yong, Zhu Xiaodong, Sun Huichuan, Shi Yinghong, Peng MinJie, Wang Xiaoying, Huang Cheng, Ding Zhenbin, He Yifeng, Shen Yinghao, Xu Yongfeng, Xiao Yongsheng, Hu Jie, Zhou Jian, Fan Jia
Department of Hepatobiliary Surgery and Liver Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China; Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China; The Longevity and Aging Institute of Fudan University, Shanghai, China.
Department of Hepatobiliary Surgery and Liver Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.
Lancet Oncol. 2025 Aug 29. doi: 10.1016/S1470-2045(25)00376-6.
The optimal conversion regimen that allows more patients with unresectable biliary tract cancer to access surgery remains unclear; there is currently no standard conversion therapy for biliary tract cancer in China, with commonly used regimens including immunotherapy-based combinations and local therapy. The ZSAB-TransGOLP study aimed to assess the efficacy and safety of tislelizumab plus lenvatinib and GEMOX (gemcitabine plus oxaliplatin) chemotherapy (GOLP) in patients with this disease.
This single-arm, phase 2 study was conducted at two centres in China. Eligible patients aged 18-70 years with previously untreated locally advanced unresectable biliary tract cancer (intrahepatic cholangiocarcinoma, perihilar bile duct cancer, and gallbladder cancer), and an Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of A, and at least 3 months' life expectancy were enrolled. Patients received 200 mg intravenous tislelizumab on day 1 and intravenous GEMOX (0·5 h of 1000 mg/m gemcitabine on days 1 and 8; and 2 h of 85 mg/m oxaliplatin on day 1) in a 21-day cycle for three cycles, and 8 mg oral lenvatinib once daily. Tumour resectability was determined by the multidisciplinary team every 3 cycles of conversion therapy; patients who were ineligible for R0 resection and did not require surgery after six cycles received maintenance therapy with tislelizumab plus lenvatinib at the same dose as used in conversion therapy until completing 1 year of treatment, disease progression, intolerable toxicity, death, consent withdrawal, or investigators' decisions. The primary endpoint was the R0 resection rate. All treated patients were evaluable for safety and primary endpoint. The trial is registered with ClinicalTrials.gov (NCT05156788) and is ongoing but closed for recruitment.
Between Dec 27, 2021 and July 3, 2023, 52 patients were screened, 11 were excluded for ineligiblity, and 41 patients were enrolled and received the GOLP regimen. All patients were Chinese, with median age of 58 years (IQR 54-65); 21 patients (51%) were male and 20 patients (49%) were female. Median duration of GOLP treatment was 3 cycles (IQR 3-6). 28 (68%) of 41 patients underwent surgery. At a median follow-up of 19·5 months (IQR 14·6-25·0) by data cutoff on Jan 20, 2025, the R0 resection rate was 63% (26 of 41 [95% CI 47-78]). All patients had at least one any-grade treatment-related adverse event (TRAE); grade 3-4 TRAEs occurred in 20 (49%) of 41 patients, with neutropenia (14 [34%] of 41) being most common. Serious TRAEs occurred in 4 (10%) of patients and included neutropenia (three [7%]) and decreased platelet count (one [2%]). No TRAE-related deaths occurred.
With promising efficacy and manageable safety, GOLP represents a potentially feasible and high-efficiency conversion regimen for unresectable locally advanced biliary tract cancer.
Program of Shanghai Academic Research Leader, the Key Disease Joint Research Program of Xuhui District, Shanghai Health Commission Clinical Research Special Project, Fellowship from the China Postdoctoral Science Foundation, National Science and Technology Major Project of China, the Outstanding Resident Clinical Postdoctoral Program of Zhongshan Hospital Affiliated to Fudan University, National Natural Science Foundation of China, and the Shanghai Sailing Program.
能让更多不可切除的胆管癌患者接受手术的最佳转化治疗方案仍不明确；目前中国尚无胆管癌的标准转化治疗方案，常用方案包括基于免疫疗法的联合方案和局部治疗。ZSAB-TransGOLP研究旨在评估替雷利珠单抗联合仑伐替尼及GEMOX（吉西他滨联合奥沙利铂）化疗（GOLP）用于该病患者的疗效和安全性。
这项单臂2期研究在中国的两个中心开展。纳入年龄在18至70岁之间、先前未经治疗的局部晚期不可切除胆管癌（肝内胆管癌、肝门部胆管癌和胆囊癌）患者，东部肿瘤协作组体能状态为0或1，Child-Pugh评分为A级，预期生存期至少3个月。患者在第1天接受200mg静脉注射替雷利珠单抗，并接受静脉注射GEMOX（第1天和第8天1000mg/m²吉西他滨静脉滴注0.5小时；第1天85mg/m²奥沙利铂静脉滴注2小时），每21天为1个周期，共3个周期，同时每日口服8mg仑伐替尼。每3个周期的转化治疗后由多学科团队确定肿瘤的可切除性；不符合R0切除标准且在6个周期后不需要手术的患者接受替雷利珠单抗联合仑伐替尼维持治疗，剂量与转化治疗相同，直至完成1年治疗、疾病进展、出现不可耐受的毒性、死亡、撤回同意或由研究者决定。主要终点为R0切除率。所有接受治疗的患者均对安全性和主要终点进行评估。该试验已在ClinicalTrials.gov注册（NCT05156788），正在进行但已停止招募。
2021年12月27日至2023年7月3日期间，共筛查52例患者，11例因不符合标准被排除，41例患者入组并接受GOLP方案治疗。所有患者均为中国人，中位年龄58岁（四分位间距54 - 65岁）；21例（51%）为男性，20例（49%）为女性。GOLP治疗的中位疗程为3个周期（四分位间距3 - 6个周期）。41例患者中有28例（68%）接受了手术。截至2025年1月20日数据截止时，中位随访19.5个月（四分位间距14.6 - 25.0个月），R0切除率为63%（41例中的26例[95%CI 47 - 78]）。所有患者均至少发生1次任何级别的治疗相关不良事件（TRAE）；41例患者中有20例（49%）发生3 - 4级TRAE，其中中性粒细胞减少最为常见（41例中的14例[34%]）。4例（10%）患者发生严重TRAE，包括中性粒细胞减少（3例[7%]）和血小板计数降低（1例[2%]）。未发生与TRAE相关的死亡。
GOLP方案疗效良好且安全性可控，是不可切除局部晚期胆管癌一种潜在可行且高效的转化治疗方案。
上海市优秀学术带头人计划、上海市徐汇区重点疾病联合研究项目、上海市卫生健康委员会临床研究专项、中国博士后科学基金资助项目、国家科技重大专项、复旦大学附属中山医院优秀住培临床博士后项目、国家自然科学基金、上海市扬帆计划。
