Local plus systemic therapies improve survival in HCC with HV/IVC invasion

Combination therapy using yttrium 90 (Y90) radioembolization and sorafenib/nivolumab for patients with hepatocellular carcinoma (HCC), with hepatic vein (HV) or inferior vena cava (IVC) invasion, results in better outcomes, as indicated by increased response rates, overall survival (OS), and progression-free survival (PFS) benefits, a study has found.

“This review of literature suggests that the combination of systemic (sorafenib or nivolumab) and local therapy (Y90 radioembolization) is effective and safe in patients with HCC-HV/IVC,” the researchers said. “However, the majority of literature on this topic comprises small studies and case reports which limit generalizable conclusions.”

Using the databases of Medline and Google Scholar, researchers in Australia and Singapore conducted a literature search for relevant articles published from 2010 to 2021. They identified 173 articles during the initial search, but 81 were excluded during abstract screening.

Furthermore, 83 articles did not have data on HV or IVC invasion and were thus excluded as well. Overall, nine articles met the inclusion criteria for data synthesis.

Some 37 patients with HV or IVC invasion had been identified from the eligible studies. Of these, 31 received sorafenib, seven nivolumab, and one both sorafenib and nivolumab. Twenty-one of the 37 patients had HV invasion, 22 had IVC invasion, and six had both HV and IVC invasion. [Proc Singap Healthc 2023;doi:10.1177/20101058231154666]

The combination of local and systemic therapies showed improved outcomes, with a median OS of 22.55 months and median PFS of 8.18 months. For these results, 23 patients were assessed using the modified RECIST criteria, while 14 were evaluated using RECIST 1.1.

Noninvasive option

“Patients with unresectable HCC with tumour thrombosis in the HV or IVC usually have poorer survival outcomes,” the researchers said. “Systemic therapy such as sorafenib is commonly used in unresectable HCC as noninvasive options are preferred.” [Cureu 2021;doi:10.7759/cureus.14107; J Hepatol 2014;61:583-538]

The included articles demonstrated the potential effectiveness of treatment with sorafenib or nivolumab in combination with Y90 radioembolization, whose benefits included “high tumour response rates and the ability to bridge patients to liver transplantation.” [Tech Vasc Interv Radiol 2019;22:93-99]

In a study, PD-1 inhibitor nivolumab successfully promoted a robust antitumoural immune response, which complemented the immunogenic effect of Y90 radioembolization. [J Hepatocell Carcinoma 2020;7:117-131]

On the other hand, the antiangiogenic agent sorafenib normalized tumour vasculature and enhanced the delivery of oxygen to the tumour. This also complemented the immunogenic effect of Y90 radioembolization. [Cureus 2020;12:e8163]

Future studies

The current study was limited by the small sample of HCC patients with HV or IVC invasion who had undergone Y90–systemic combination therapy. In addition, the researchers did not fully explore the optimal interval and dosage of sorafenib or nivolumab when used with Y90 radioembolization.

“Therefore, future studies including multicentre trials could evaluate the role of Y90-systemic combination therapy in HCC-HV/IVC invasion,” the researchers said.

“Currently, there is considerable interest in the combination of Y90 and atezolizumab with bevacizumab. We are presently conducting a multicentre trial to study the value of this combination,” they added.