Ajmera Transplant Program, University Health Network, Toronto, Ontario, M5G 2N2, Canada.
Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2M9, Canada.
Future Oncol. 2022 Jun;18(18):2173-2191. doi: 10.2217/fon-2021-1635. Epub 2022 Mar 15.
Recurrent hepatocellular carcinoma (HCC) develops in 15-20% of liver transplant recipients, and it tends to be more aggressive due to underlying immunosuppression. The multikinase inhibitor cabozantinib has been shown to be effective for the treatment of advanced HCC. However, there is no study evaluating this medication in patients with recurrent HCC. Adult patients with measurable biopsy-proven recurrent HCC are eligible for enrollment provided they are not amenable to curative treatments and no prior treatment with cabozantinib. In this study, 60 mg once daily cabozantinib will be administered orally. Participants will receive study treatment as long as they continue to experience clinical benefit or until there is unacceptable toxicity. Tumor measurements will be repeated every 8 weeks to evaluate response. The primary end point of this study will be the disease control rate at 4 months after treatment. The secondary end points will be overall survival, progression-free survival and safety profile of cabozantinib. Furthermore, potential biomarkers will be evaluated to identify their role in tumor progression. The total duration of this trial is expected to be 3 years. We anticipate that this trial will show the effectiveness and safety of cabozantinib in the treatment of post-liver transplant recurrent HCC. Cabozantinib is expected to be an effective treatment due to its activity against many protein kinases, including MET and AXL which are not inhibited by sorafenib.
复发性肝细胞癌 (HCC) 在 15-20%的肝移植受者中发展，由于潜在的免疫抑制，其往往更具侵袭性。多激酶抑制剂卡博替尼已被证明可有效治疗晚期 HCC。然而，尚无研究评估该药在复发性 HCC 患者中的应用。对于经活检证实的可测量复发性 HCC 成年患者，如果不能进行根治性治疗且无卡博替尼治疗史，则有资格入组。在这项研究中，每天口服 60mg 卡博替尼。只要患者继续有临床获益或出现不可接受的毒性，将继续接受研究治疗。每 8 周重复肿瘤测量以评估反应。该研究的主要终点是治疗后 4 个月的疾病控制率。次要终点是卡博替尼的总生存期、无进展生存期和安全性。此外，还将评估潜在的生物标志物，以确定它们在肿瘤进展中的作用。该试验的总持续时间预计为 3 年。我们预计，该试验将显示卡博替尼在治疗肝移植后复发性 HCC 中的有效性和安全性。卡博替尼有望成为一种有效的治疗药物，因为它可抑制多种蛋白激酶，包括索拉非尼不能抑制的 MET 和 AXL。
