Li Jingjing, Zhou Shurui, Xu Xiaoqing, Zheng Qinhong, Zhang Fabiao, Luo Cong, Li Da, Sun Xing, Han Zhe, Wu Wei, Yan Junrong, Shao Yang, Zhang Yuhua, Wu Bingchen, Wei Qing, Wang Xinbao, Zhou Yiwen, Sun Weijing, Xu Qi, Ying Jieer
Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, PR China.
Nat Commun. 2025 Jul 1;16(1):5559. doi: 10.1038/s41467-025-60119-3.
Biliary tract cancer (BTC) has a poor prognosis with limited treatment options. This phase 2 trial randomized 80 patients with unresectable/metastatic BTC 1:1 to sintilimab, anlotinib, and gemcitabine/cisplatin (SAGC) or chemotherapy alone (GC). At 13.4-month median follow-up, SAGC significantly improved median progression-free survival (8.5 vs. 6.3 months; HR 0.48, 95% CI 0.22-0.64, p = 0.005) and objective response rate (51.4% vs. 29.4%), with higher grade 3/4 adverse events (75.0% vs. 43.6%). Post hoc analysis showed enhanced efficacy with anlotinib 8 mg versus 10 mg (ORR 54.5% vs. 38.8%). In AKT/YAP tumor models, low-dose anlotinib (3 mg/kg) combined with sintilimab improved vascular perfusion, T-cell cytotoxicity, and cytokine secretion compared to high-dose (6 mg/kg). These findings demonstrate improved efficacy and manageable toxicity with SAGC, particularly at the 8 mg anlotinib dose, suggesting low-dose regimens may optimize antitumor response while mitigating adverse effects. Trial registration number ClinicalTrials.gov Identifier: NCT04300959.
胆道癌（BTC）预后较差，治疗选择有限。这项2期试验将80例不可切除/转移性BTC患者按1:1随机分为信迪利单抗、安罗替尼联合吉西他滨/顺铂（SAGC）组或单纯化疗（GC）组。在13.4个月的中位随访期，SAGC组显著改善了中位无进展生存期（8.5个月对6.3个月；风险比0.48，95%置信区间0.22 - 0.64，p = 0.005）和客观缓解率（51.4%对29.4%），但3/4级不良事件发生率更高（75.0%对43.6%）。事后分析显示，8毫克安罗替尼组比10毫克组疗效更佳（客观缓解率54.5%对38.8%）。在AKT/YAP肿瘤模型中，与高剂量（6毫克/千克）相比，低剂量安罗替尼（3毫克/千克）联合信迪利单抗可改善血管灌注、T细胞细胞毒性和细胞因子分泌。这些发现表明SAGC方案疗效更佳且毒性可控，尤其是8毫克安罗替尼剂量时，提示低剂量方案可能在减轻不良反应的同时优化抗肿瘤反应。试验注册号：ClinicalTrials.gov标识符：NCT04300959。
