卡博替尼在最新实际临床实践中治疗晚期肝细胞癌：一项多中心回顾性分析

Cabozantinib for Advanced Hepatocellular Carcinoma in the Latest Real-World Practice: A Multicenter Retrospective Analysis.

作者信息

Kanzaki Hiroaki, Ogasawara Sadahisa, Okubo Tomomi, Itokawa Norio, Yoshino Ryohei, Fujimoto Kentaro, Kogure Tadayoshi, Yumita Sae, Ishino Takamasa, Ogawa Keita, Iwanaga Terunao, Nakagawa Miyuki, Fujiwara Kisako, Kojima Ryuta, Koroki Keisuke, Inoue Masanori, Kobayashi Kazufumi, Kanogawa Naoya, Kiyono Soichiro, Nakamura Masato, Kondo Takayuki, Nakagawa Ryo, Nakamoto Shingo, Muroyama Ryosuke, Itobayashi Ei, Atsukawa Masanori, Kato Jun, Kato Naoya

机构信息

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan.

Department of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan.

出版信息

Drugs Real World Outcomes. 2023 Dec;10(4):513-520. doi: 10.1007/s40801-023-00379-x. Epub 2023 Jul 19.

DOI:10.1007/s40801-023-00379-x

PMID:37466822

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10730490/

Abstract

BACKGROUND

Cabozantinib was found to be effective as a second- or third-line treatment after sorafenib in patients with advanced hepatocellular carcinoma (HCC) in the phase 3 CELESTIAL trial. So far, as immunotherapy has substituted molecular target agents as the primary systemic therapy for advanced HCC, cabozantinib is extensively used in the latest real-world clinical practice in a greatly different position than that shown by the CELESTIAL trial. In the current analysis, we examined the safety and effectiveness of cabozantinib administration in real-life settings for patients with advanced HCC.

METHODS

We retrospectively obtained data from patients with advanced HCC who received cabozantinib in three institutions in Japan between 14 September 2018 and 30 November 2021.

RESULTS

During the study period, 23 patients with advanced HCC received cabozantinib. Our cohort included 21.7% of patients with Child-Pugh class B, and 52.2% of patients in fourth line or later. The median progression-free survival of patients given cabozantinib was 3.7 months. Regarding patients with Child-Pugh class B or administration in fourth line or later, the discontinuation rate due to adverse events in patients who initialized at 40 or 20 mg was lower than those who initialized at 60 mg (42.9% versus 75.0%). Patients who were able to continue treatment with cabozantinib for more than 3 months were more likely to undergo dose reduction than those who did not (85.7% versus 25.0%).

CONCLUSIONS

Cabozantinib has recently been administered to a diverse range of patients, including those who were not enrolled in the CELESTIAL trial. Deliberate dose reduction could potentially offer clinical benefits to patients with impaired liver function. Furthermore, managing adverse events by reducing the dose could play a crucial role in extending the duration of treatment with cabozantinib. The preprint version of this work is available on https://www.researchsquare.com/article/rs-2655181/v1 .

摘要

背景

在3期CELESTIAL试验中，卡博替尼被发现对晚期肝细胞癌（HCC）患者在索拉非尼治疗后作为二线或三线治疗有效。到目前为止，由于免疫疗法已取代分子靶向药物成为晚期HCC的主要全身治疗方法，卡博替尼在最新的实际临床实践中的广泛应用与CELESTIAL试验所显示的情况有很大不同。在本次分析中，我们研究了卡博替尼在晚期HCC患者实际治疗中的安全性和有效性。

方法

我们回顾性收集了2018年9月14日至2021年11月30日期间在日本三个机构接受卡博替尼治疗的晚期HCC患者的数据。

结果

在研究期间，23例晚期HCC患者接受了卡博替尼治疗。我们的队列包括21.7%的Child-Pugh B级患者和52.2%的四线及以后治疗的患者。接受卡博替尼治疗的患者的中位无进展生存期为3.7个月。对于Child-Pugh B级患者或四线及以后治疗的患者，初始剂量为40或20 mg的患者因不良事件停药率低于初始剂量为60 mg的患者（42.9%对75.0%）。能够继续使用卡博替尼治疗超过3个月的患者比不能继续治疗的患者更有可能进行剂量减少（85.7%对25.0%）。

结论

卡博替尼最近已应用于包括未参加CELESTIAL试验的患者在内的各种患者。有意降低剂量可能会给肝功能受损的患者带来临床益处。此外，通过降低剂量管理不良事件可能在延长卡博替尼治疗持续时间方面发挥关键作用。这项工作的预印本版本可在https://www.researchsquare.com/article/rs-2655181/v1上获取。