Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
Department of Hematology/Oncology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
J Cancer Res Clin Oncol. 2023 Aug;149(10):7547-7555. doi: 10.1007/s00432-023-04704-3. Epub 2023 Mar 27.
PURPOSE: Immune checkpoint inhibitors (ICIs) have been demonstrated to be effective for unresectable or metastatic hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA) in prior prospective trials. However, the clinical outcomes of ICIs in patients with combined HCC-CCA (cHCC-CCA) have not been investigated. Accordingly, we retrospectively evaluated the effectiveness and safety of ICIs in patients with unresectable or metastatic cHCC-CCA. METHODS: Among 101 patients with histologically documented cHCC-CCA who received systemic therapy, 25 received ICIs between January 2015 and September 2021 and were included in the current analysis. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were retrospectively evaluated. RESULTS: The median age was 64 years (range 38-83) and 84% (n = 21) of patients were males. Most patients had Child-Pugh A liver function (n = 22, 88%) and hepatitis B virus infection (17, 68%). Nivolumab (n = 17, 68%) was the most frequently used ICI, followed by pembrolizumab (n = 5, 20%), atezolizumab plus bevacizumab (n = 2, 8%), and ipilimumab plus nivolumab (n = 1, 4%). All patients, except one, had previously received systemic therapy; median two lines (1-5 lines) of systemic therapy were administered prior to ICIs. With a median follow-up duration of 20.1 months (95% CI 4.9-35.2 months), the median PFS was 3.5 months (95% CI 2.4-4.8 months), and the median OS was 8.3 months (95% CI 6.8-9.8 months). The ORR was 20.0% (n = 5, nivolumab for 2 patients, pembrolizumab for 1, atezolizumab plus bevacizumab for 1, and ipilimumab plus nivolumab for 1) and the duration of response was 11.6 months (95% CI 11.2-12.0 months). CONCLUSIONS: ICIs displayed clinical anti-cancer effectiveness, aligning with the results of prior prospective studies for HCC or CCA. Further international studies are required to define the optimal strategies for managing unresectable or metastatic cHCC-CCA.
目的：免疫检查点抑制剂（ICI）在之前的前瞻性试验中已被证明对不可切除或转移性肝细胞癌（HCC）或胆管癌（CCA）有效。然而，ICI 在合并 HCC-CCA（cHCC-CCA）患者中的临床结果尚未得到研究。因此，我们回顾性评估了 ICI 对不可切除或转移性 cHCC-CCA 患者的疗效和安全性。
方法：在 101 名接受组织学证实的 cHCC-CCA 系统治疗的患者中，25 名患者在 2015 年 1 月至 2021 年 9 月期间接受了 ICI 治疗，并纳入本研究。回顾性评估了根据实体瘤反应评价标准（RECIST）1.1 版评估的总体缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和不良事件（AE）。
结果：中位年龄为 64 岁（范围 38-83 岁），84%（n=21）的患者为男性。大多数患者肝功能为 Child-Pugh A 级（n=22，88%）和乙型肝炎病毒感染（n=17，68%）。纳武单抗（n=17，68%）是最常使用的 ICI，其次是派姆单抗（n=5，20%）、阿替利珠单抗联合贝伐珠单抗（n=2，8%）和伊匹单抗联合纳武单抗（n=1，4%）。除 1 例患者外，所有患者均接受过系统治疗；ICI 治疗前，中位数为 2 线（1-5 线）系统治疗。中位随访时间为 20.1 个月（95%CI 4.9-35.2 个月），中位 PFS 为 3.5 个月（95%CI 2.4-4.8 个月），中位 OS 为 8.3 个月（95%CI 6.8-9.8 个月）。ORR 为 20.0%（n=5，纳武单抗 2 例，派姆单抗 1 例，阿替利珠单抗联合贝伐珠单抗 1 例，伊匹单抗联合纳武单抗 1 例），缓解持续时间为 11.6 个月（95%CI 11.2-12.0 个月）。
结论：ICI 显示出临床抗癌疗效，与 HCC 或 CCA 的前瞻性研究结果一致。需要进一步的国际研究来确定治疗不可切除或转移性 cHCC-CCA 的最佳策略。
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