Department of Medical Oncology, Austin Health, Melbourne, Australia.
Olivia Newton-John Cancer Research Institute, Melbourne, Australia.
JAMA Oncol. 2020 Sep 1;6(9):1405-1409. doi: 10.1001/jamaoncol.2020.2814.
Biliary tract cancers represent a rare group of malignant conditions with very limited treatment options. Patients with advanced disease have a poor outcome with current therapies.
To evaluate the efficacy and safety of combination immunotherapy with nivolumab and ipilimumab in patients with advanced biliary tract cancers.
DESIGN, SETTING, AND PARTICIPANTS: The CA209-538 prospective multicenter phase 2 nonrandomized clinical trial included patients with advanced rare cancers including patients with biliary tract cancers. This subgroup analysis evaluated 39 patients from CA209-538 with biliary tract cancers who were enrolled from December 2017 to December 2019. Most of the patients (n = 33) had experienced disease progression after 1 or more lines of therapy and had tumor tissue available for biomarker research.
Patients received treatment with nivolumab at a dose of 3 mg/kg and ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg every 2 weeks and continued for up to 96 weeks until disease progression or the development of unacceptable toxic events.
The primary end point was disease control rate (complete remission, partial remission, or stable disease) as assessed by RECIST 1.1.
Among the 39 patients included in this subgroup analysis of a phase 2 clinical trial (20 men, 19 women; mean [range] age, 65 [37-81] years), the objective response rate was 23% (n = 9) with a disease control rate of 44% (n = 17); all responders had received prior chemotherapy, and none had a microsatellite unstable tumor. Responses were exclusively observed in patients with intrahepatic cholangiocarcinoma and gallbladder carcinoma. The median duration of response was not reached (range, 2.5 to ≥23 months). The median progression-free survival was 2.9 months (95% CI, 2.2-4.6 months), and overall survival was 5.7 months (95% CI, 2.7-11.9 months). Immune-related toxic events were reported in 49% of patients (n = 19), with 15% (n = 6) experiencing grade 3 or 4 events.
This subgroup analysis of a phase 2 clinical trial found that combination immunotherapy with nivolumab and ipilimumab was associated with substantial positive outcomes patients with advanced biliary tract cancers. This treatment compares favorably to single-agent anti-programmed cell death protein 1 (anti-PD-1) therapy and warrants further investigation. Ongoing translational research is focused on identifying biomarkers that can predict treatment response.
ClinicalTrials.gov Identifier: NCT02923934.
胆道癌是一组罕见的恶性疾病，治疗选择非常有限。晚期疾病患者的预后很差，现有疗法的疗效有限。
评估纳武单抗联合伊匹单抗联合治疗晚期胆道癌患者的疗效和安全性。
设计、地点和参与者：CA209-538 前瞻性多中心 2 期非随机临床研究纳入了包括胆道癌患者在内的晚期罕见癌症患者。这项亚组分析评估了 39 名来自 CA209-538 的胆道癌患者，他们于 2017 年 12 月至 2019 年 12 月期间入组。大多数患者（n=33）在接受 1 种或多种治疗后疾病进展，并可获得肿瘤组织进行生物标志物研究。
患者接受纳武单抗 3 mg/kg 和伊匹单抗 1 mg/kg 每 3 周治疗 4 个剂量，随后纳武单抗 3 mg/kg 每 2 周治疗，持续 96 周，直至疾病进展或发生不可接受的毒性事件。
主要终点为根据 RECIST 1.1 评估的疾病控制率（完全缓解、部分缓解或疾病稳定）。
在这项 2 期临床试验的亚组分析中（20 名男性，19 名女性；平均[范围]年龄 65[37-81]岁），39 名患者中客观缓解率为 23%（n=9），疾病控制率为 44%（n=17）；所有缓解者均接受过化疗，无一例为微卫星不稳定肿瘤。反应仅在肝内胆管癌和胆囊癌患者中观察到。缓解持续时间未达到（范围 2.5 至≥23 个月）。中位无进展生存期为 2.9 个月（95%CI，2.2-4.6 个月），总生存期为 5.7 个月（95%CI，2.7-11.9 个月）。49%的患者（n=19）出现免疫相关毒性事件，15%（n=6）发生 3 级或 4 级事件。
这项 2 期临床试验的亚组分析发现，纳武单抗联合伊匹单抗联合治疗晚期胆道癌患者具有显著的积极疗效。这种治疗方法与单药抗程序性死亡蛋白 1（抗 PD-1）治疗相比具有优势，值得进一步研究。正在进行的转化研究侧重于确定可预测治疗反应的生物标志物。
ClinicalTrials.gov 标识符：NCT02923934。
