Department of Bio-therapeutic, the First Medical Center, Chinese PLA General Hospital, Beijing, China.
Department of Geriatric Hematology, the Second Medical Center, Chinese PLA General Hospital, Beijing, China.
J Immunother Cancer. 2020 Jun;8(1). doi: 10.1136/jitc-2019-000367.
The prognosis of patients with unresectable or metastatic biliary tract cancer (BTC) is unacceptably low. This study aimed to determine the efficacy, safety and predictive biomarkers of the immune checkpoint inhibitor nivolumab in combination with chemotherapy in advanced BTCs.
In this open-label, single-arm, phase II trial, a chemotherapy and immunotherapy combination consisting of gemcitabine 1000 mg/m, cisplatin 75 mg/m and nivolumab 3 mg/kg was administered every 3 weeks for up to six cycles. Maintenance treatment with gemcitabine plus nivolumab was administered to patients achieving disease control following the combination therapy. The primary outcome was the objective response rate. Secondary outcomes included safety, disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). The exploratory objective was to assess biomarkers for predicting clinical response and prognosis.
Thirty-two patients with a median age of 60 (range 27-69) years were enrolled. As of September 31, 2019, the median follow-up was 12.8 (95% CI 10.8 to 14.8) months. Twenty-seven response-evaluable patients received a median of 4 (IQR, 3-6) cycles of combination therapy, of whom 15 (55.6%) patients achieved an objective response, including 5 (18.6%) with a complete response (CR), and the DCR was 92.6%. Of the six patients in cohort A who were resistant to gemcitabine-based or cisplatin-based chemotherapy, one achieved CR and one achieved partial response. Thirteen of 21 chemotherapy-naive patients (61.9%) in cohort B achieved an objective response. The median PFS of all patients in cohorts A+B was 6.1 months. The median OS was 8.5 months, with a 33.3% 12-month OS rate. The most frequent grade 3 or higher adverse events were thrombocytopenia (56%) and neutropenia (22%). Fitness might be a biomarker for predicting clinical response. On-therapy changes in serum soluble FasL, MCP-1 and interferon-γ were correlated with prognosis.
Nivolumab in combination with gemcitabine and cisplatin offers promising efficacy and a manageable safety profile for patients with advanced BTCs.
NCT03311789.
不可切除或转移性胆道癌（BTC）患者的预后极差。本研究旨在确定免疫检查点抑制剂纳武利尤单抗联合化疗在晚期 BTC 中的疗效、安全性和预测生物标志物。
在这项开放标签、单臂、Ⅱ期试验中，采用吉西他滨 1000mg/m2、顺铂 75mg/m2 和纳武利尤单抗 3mg/kg 的化疗和免疫治疗联合方案，每 3 周给药 1 次，最多 6 个周期。在联合治疗后达到疾病控制的患者接受吉西他滨联合纳武利尤单抗维持治疗。主要终点为客观缓解率。次要终点包括安全性、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。探索性目的是评估预测临床反应和预后的生物标志物。
共纳入 32 例中位年龄为 60 岁（范围 27-69 岁）的患者。截至 2019 年 9 月 31 日，中位随访时间为 12.8（95%CI 10.8-14.8）个月。27 例可评估疗效的患者接受了中位数为 4（IQR，3-6）个周期的联合治疗，其中 15 例（55.6%）患者获得了客观缓解，包括 5 例（18.6%）完全缓解（CR），DCR 为 92.6%。在对吉西他滨为基础或顺铂为基础的化疗耐药的 6 例 A 队列患者中，1 例获得 CR，1 例获得部分缓解。在 B 队列的 21 例化疗初治患者中，13 例（61.9%）获得了客观缓解。A+B 队列的所有患者的中位 PFS 为 6.1 个月。中位 OS 为 8.5 个月，12 个月 OS 率为 33.3%。最常见的 3 级或更高级别的不良事件为血小板减少症（56%）和中性粒细胞减少症（22%）。体能可能是预测临床反应的生物标志物。治疗期间血清可溶性 FasL、MCP-1 和干扰素-γ的变化与预后相关。
纳武利尤单抗联合吉西他滨和顺铂为晚期 BTC 患者提供了有前景的疗效和可管理的安全性。
NCT03311789。
