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Editor's note
Hepatocellular carcinoma (HCC) is one of the leading causes of malignancy-related mortality worldwide, and the occurrence and progression of tumors are often accompanied by difficult sequelae. Portal vein cancer thrombosis (PVTT) is one of the common complications of HCC, with an incidence of 44%~62%. However, as the recommended standard of care for HCC with PVTT, sorafenib prolongs survival by only nearly 2 months.
近日，暨南大学附属第一医院介入与血管科李承志教授团队在Hepatology Intertional杂志发表题为“Hepatic artery infusion chemotherapy combined with camrelizumab plus rivoceranib for hepatocellular carcinoma with portal vein tumor thrombosis: a multicenter propensity score‑matching analysis”的研究论文，探讨了HCC伴PVTT联合疗法的有效性和安全性，为HCC 伴PVTT的治疗提供了广阔前景。
Background:
PVTT is a marker of advanced HCC and is associated with a high risk of progression and a poor prognosis. As standard of care, sorafenib monotherapy has limited efficacy in HCC with PVTT.
Currently, a combination of antithrombotic and immunotherapy regimens is widely considered to be the treatment for advanced HCC with or without PVTT and is more effective than oral sorafenib. In two previous randomized controlled trials (RCTs), IMBRAVE-150 and KEYNOTE-524, antithrombotic therapy and PD-1/PD-L1 inhibitors have shown promising prospects. In view of the impressive results of previous clinical studies, camrelizumab and apatinib have demonstrated significant efficacy in both tumor management and adverse reaction control as second-line treatments for patients with pre-treated advanced HCC.
Transarterial cannulation chemoembolization (TACE) is generally considered the standard treatment for advanced HCC; However, efficacy in the treatment of patients with HCC and PVTT is often limited. Hepatic arterial perfusion chemotherapy (HAIC) is a catheter-based local treatment that, unlike traditional systemic chemotherapy, reduces treatment-related adverse effects while delivering high concentrations of drugs locally. A recent phase III randomized trial demonstrated that HAIC is a better option than TACE for HCC patients with high tumor burden. According to Chinese guidelines, HAIC monotherapy and combination therapy have been recommended as the best treatment for advanced HCC with severe PVTT.
On the other hand, the advantages and adverse effects of HAIC in improving the efficacy of systemic therapy in patients with HCC with or without PVTT have been widely demonstrated in multiple retrospective studies. Therefore, the combination of HAIC and targeted + immunotherapy is expected to further improve the survival rate of HCC patients with PVTT.
Research Methods:
The study included patients with HCC with PVTT who received HAIC in combination with camrelizumab and apatinib triple therapy (HAICCR group) or camrelizumab and apatinib dual therapy (CR group) as first-line therapy between January 2020 and December 2021, during which all subjects were eligible-checked at four hospital centers in mainland China. In order to balance any differences between groups, the investigators used propensity score matching (PSM).
Findings:
In this study, a total of 411 patients received either triple therapy (HAICCR group, n=292) or dual therapy (CR group, n=119) between January 2020 and December 2021. The results showed that overall survival (mOS: 19.60 months vs. 11.50 months, P<0.0001) and progression-free survival (mPFS: 10.0 months vs. 5.6 months, P<0.0001) were significantly improved in the HAICCR group compared with the CR group. In addition, the objective response rate (ORR: 55.5% vs. 42.0%, P=0.013) and disease control rate (DCR: 89.0% vs. 79.0%, P=0.008) were also significantly higher in the HAICCR group. After PSM, 83 pairs of final matched cohorts were obtained, and the survival-benefit analysis of this cohort yielded consistent results (mOS: 18.70 months vs. 11.0 months, P<0.0001; mPFS: 10.0 months vs. 5.6 months, P<0.0001). However, there was no significant difference in ORR between triple and dual therapy.
Table 1. Optimal tumor response before and after PSM
Univariate and multivariate analyses showed that Child-Turcotte-Pugh (CTP) stage, albumin-bilirubin index (ALBI) grade, number of tumors, and treatment regimen were important risk factors for OS, while alpha-fetoprotein (AFP) level, number of tumors, metastasis, and treatment regimen were important risk factors for PFS. In terms of safety, hypertension and hand-foot syndrome were the two most common adverse reactions, and there was no significant difference in the incidence of adverse reactions between the two groups (P<0.05).
Conclusions of the study
In the setting of HCC with PVTT, the HAIC and camrelizumab plus apatinib triple regimens demonstrated superior survival benefit and were well tolerated and safely compared with camrelizumab plus apatinib. This triple therapy has great promise and great potential in the treatment of advanced HCC with PVTT.
参考文献：Li,Y.,Guo,J.,Liu,W.et al. Hepatic artery infusion chemotherapy combined with camrelizumab plus rivoceranib for hepatocellular carcinoma with portal vein tumor thrombosis: a multicenter propensity score-matching analysis. Hepatol Int (2024).
https://doi.org/10.1007/s12072-024-10672-8
Source: Editorial Board of International Liver Disease