度伐利尤单抗/替西木单抗在阿替利珠单抗/贝伐珠单抗治疗后作为免疫检查点抑制剂再次挑战用于不可切除肝细胞癌的疗效和安全性。
Efficacy and Safety of Durvalumab/Tremelimumab in Unresectable Hepatocellular Carcinoma as Immune Checkpoint Inhibitor Rechallenge Following Atezolizumab/Bevacizumab Treatment.
机构信息
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Laboratory of Molecular and Cellular Medicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
出版信息
Target Oncol. 2024 Sep;19(5):769-778. doi: 10.1007/s11523-024-01092-7. Epub 2024 Sep 2.
BACKGROUND
While guidelines recommend immune checkpoint inhibitor (ICI) rechallenge as second-line therapy for unresectable hepatocellular carcinoma (HCC), data supporting this remain limited, particularly regarding a standard regimen for first- and second-line treatments. Tremelimumab/durvalumab was recently approved but data on ICI rechallenge are lacking.
OBJECTIVES
The purpose of this study was to evaluate the early efficacy and safety of tremelimumab/durvalumab for HCC as an ICI rechallenge following initial ICI therapy with atezolizumab/bevacizumab.
PATIENTS AND METHODS
This multicenter retrospective study included patients with HCC who underwent treatment with tremelimumab/durvalumab, with relevant available clinical information. We evaluated the safety and efficacy of tremelimumab/durvalumab as ICI rechallenge following initial treatment with atezolizumab/bevacizumab. We analyzed the outcomes in patients who underwent tremelimumab/durvalumab as an ICI rechallenge and those who received tremelimumab/durvalumab as their initial ICI therapy RESULT: A total of 45 patients treated with tremelimumab/durvalumab were included, with 55.6% (25/45) undergoing ICI rechallenge. The objective-response and disease-control rates in patients who underwent ICI rechallenge were 14.3% (3/21) and 47.6% (10/21), respectively, similar to those in patients initially treated with tremelimumab/durvalumab. All patients (n = 3) who experienced the best response to progressive disease (PD) with initial atezolizumab/bevacizumab experienced PD during ICI rechallenge. The incidence rates of adverse events were similar between patient groups treated with tremelimumab/durvalumab as ICI rechallenge and initial ICI. Among patients experiencing immune-related adverse events (irAEs) with atezolizumab/bevacizumab, 75% (3/4) encountered similar irAEs during ICI rechallenge.
CONCLUSION
Early safety and efficacy profiles of durvalumab/tremelimumab as ICI rechallenge are satisfactory.
背景
虽然指南建议将免疫检查点抑制剂（ICI）重新用于不可切除的肝细胞癌（HCC）作为二线治疗，但支持这一建议的数据仍然有限，特别是对于一线和二线治疗的标准方案。Tremelimumab/durvalumab 最近获得批准，但缺乏 ICI 重新挑战的数据。
目的
本研究旨在评估 Tremelimumab/durvalumab 作为阿替利珠单抗/贝伐珠单抗初始 ICI 治疗后 HCC 的 ICI 重新挑战的早期疗效和安全性。
患者和方法
这是一项多中心回顾性研究，纳入了接受 Tremelimumab/durvalumab 治疗且有相关临床资料的 HCC 患者。我们评估了 Tremelimumab/durvalumab 作为阿替利珠单抗/贝伐珠单抗初始治疗后 ICI 重新挑战的安全性和疗效。我们分析了接受 Tremelimumab/durvalumab 作为 ICI 重新挑战的患者和作为初始 ICI 治疗的患者的结局。
结果
共纳入 45 例接受 Tremelimumab/durvalumab 治疗的患者，其中 55.6%（25/45）接受 ICI 重新挑战。接受 ICI 重新挑战的患者的客观缓解率和疾病控制率分别为 14.3%（21/143）和 47.6%（21/45），与初始接受 Tremelimumab/durvalumab 治疗的患者相似。所有在初始阿替利珠单抗/贝伐珠单抗治疗时对进展性疾病（PD）反应最佳的患者（n=3）在 ICI 重新挑战时均出现 PD。接受 Tremelimumab/durvalumab 作为 ICI 重新挑战和初始 ICI 治疗的患者的不良事件发生率相似。在接受阿替利珠单抗/贝伐珠单抗治疗时发生免疫相关不良事件（irAEs）的患者中，75%（3/4）在 ICI 重新挑战时出现相似的 irAEs。
结论
Durvalumab/tremelimumab 作为 ICI 重新挑战的早期安全性和疗效特征令人满意。
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