Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer Med. 2023 Jun;12(11):12263-12271. doi: 10.1002/cam4.5924. Epub 2023 Apr 11.
This study was aimed to evaluate the safety and the efficacy of gemcitabine and oxaliplatin (GEMOX) combined with donafenib plus tislelizumab as the first-line treatment for patients with unresectable biliary tract cancer (BTC).
This is a prospective single-center exploratory study. Eligible patients (Stage III/IV BTC, at least one measurable disease according to RECIST v1.1, etc.) received gemcitabine 1000 mg/m IV Q3W, oxaliplatin 100 mg/m IV Q3W, donafenib 200 mg PO BID, and tislelizumab 200 mg IV Q3W until disease progression, unacceptable toxicity, or withdrawal of consent whichever occurred first. The primary endpoint was safety and secondary endpoints included disease control rate (DCR), objective response rate (ORR), conversion rate, and overall survival (OS).
A total of 13 patients were enrolled. The median follow-up time was 420 days (range 345-487). The median duration of treatment was four cycles (range 1-15). The incidence of ≥Grade 3 treatment-related adverse events (TRAEs) was 53.8% and no Grade 5 TRAE. The most frequent Grade 3-4 TRAEs were rash (4/13, 30.8%), platelet count decreased (2/13, 15.4%), and fatigue (2/13, 15.4%). Tumor response was assessed in eight evaluable patients; ORR was 25.0% (95% CI, 3.2%-65.1%) and DCR 87.5% (95% CI, 47.3%-99.7%). The median PFS was 4.8 months (95% CI, 1.25-NE). Three Stage III patients underwent subsequent surgery with a conversion rate of 23.1%. The median OS was not estimable.
GEMOX combined with donafenib plus tislelizumab as the first-line therapy for unresectable BTC showed manageable toxicity and encouraging efficacy especially in terms of promising conversion rate in Stage III patients.
本研究旨在评估吉西他滨和奥沙利铂（GEMOX）联合多纳非尼加替雷利珠单抗作为不可切除胆管癌（BTC）患者一线治疗的安全性和疗效。
这是一项前瞻性单中心探索性研究。符合条件的患者（III/IV 期 BTC，至少有一项根据 RECIST v1.1 可测量的疾病等）接受吉西他滨 1000mg/m2 静脉滴注，Q3W；奥沙利铂 100mg/m2 静脉滴注，Q3W；多纳非尼 200mg 口服，BID；替雷利珠单抗 200mg 静脉滴注，Q3W，直至疾病进展、无法耐受的毒性或患者撤回同意书。主要终点为安全性，次要终点包括疾病控制率（DCR）、客观缓解率（ORR）、转化率和总生存期（OS）。
共纳入 13 例患者。中位随访时间为 420 天（范围 345-487）。中位治疗持续时间为四个周期（范围 1-15）。≥3 级治疗相关不良事件（TRAEs）发生率为 53.8%，无 5 级 TRAE。最常见的 3-4 级 TRAE 为皮疹（4/13，30.8%）、血小板计数减少（2/13，15.4%）和疲劳（2/13，15.4%）。在 8 例可评估患者中评估了肿瘤反应；ORR 为 25.0%（95%CI，3.2%-65.1%），DCR 为 87.5%（95%CI，47.3%-99.7%）。中位无进展生存期（PFS）为 4.8 个月（95%CI，1.25-NE）。3 例 III 期患者随后接受手术，转化率为 23.1%。中位 OS 不可估计。
吉西他滨联合奥沙利铂联合多纳非尼加替雷利珠单抗作为不可切除 BTC 的一线治疗具有可管理的毒性，疗效令人鼓舞，特别是在 III 期患者中具有较高的转化率。
