The recent global IMbrave150 study evaluated the combination of atezolizumab and bevacizumab versus sorafenib in 501 patients with advanced or metastatic Hepatocellular Carcinoma (HCC). The median overall survival (OS) was notably better in the atezolizumab/bevacizumab group. However, for HCC patients with intrahepatic macrovascular invasion (MVI), the prognosis remains poor, indicating a significant unmet need in this group.
External Beam Radiotherapy (EBRT) has shown promising results in treating HCC with MVI, especially when used in combination with trans-arterial chemoembolization (TACE). It has been reported that radiotherapy may make tumor cells more susceptible to immune-mediated therapy, potentially enhancing the effects of atezolizumab and bevacizumab.
Thus, this study aims to investigate the efficacy and safety of atezolizumab/bevacizumab alone versus atezolizumab/bevacizumab in combination with EBRT in HCC patients with macrovascular invasion.
Older than 19 years of age, lower than 80 years of age
Child-Pugh class A hepatic function
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
Patients with HCC [diagnosed according to AASLD guidelines] invading the intrahepatic vascular system
Treatment history of prior systemic treatment of HCC
Liver transplant recipients
Patients with peptic ulcer, untreated or incompletely treated varices with bleeding or high-risk for bleeding
Any serious illness (e.g., active infection or inflammatory condition) or uncontrolled severe medical comorbidity
Parallel
Atezolizumab plus bevacizumab, combined EBRT to vascular invasion
RadiationThe external beam radiotherapy will commence after day 2 of the first cycle of atezolizumab+bevacizumab, and will be delivered in accordance with institutional protocol. 3D-conformal radiotherapy technique is used to determine target volumes, radiation ports, and dose prescriptions by using a 3D radiotherapy planning system. The gross tumor volume (GTV) includes vascular invasion and a 2-cm margin into the contiguous HCC. The GTV can consist of the entire HCC and vascular invasion at the discretion of the investigator. The target dose is 45 Gy, however, the total dose can be reduced as low as 30 Gy according to the liver function, liver volumes, or the maximum dose to the stomach/duodenum during the planning process according to the judgment of the radiation oncologist of each participating sites.
Atezolizumab plus bevacizumab
DrugAtezolizumab plus bevacizumab q3w
progression-free survival rate
Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first
Overall survival rate
Randomization to death from any cause, through the end of study
Objective response
complete response or partial response as determined by the Investigator according to RECIST V1.1
Adverse reaction rate
Adverse reaction rate assessed by CTCAE version 5
Time to deterioration
The time from randomization to first deterioration (decrease from baseline of ≥10 points) in the patient-reported global health status (GHS) / Quality of life (QoL), physical function, or role function scales of the EORTC QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks
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Asan Medical Center
Lead sponsor
Seoul National University Hospital
Collaborator
Hanyang University Guri Hospital
Collaborator
Soon Chun Hyang University
Collaborator
