tace plus atezolizumab/bevacizumab and i-125 seeds brachytherapy for hcc with branch pvtt

Conditions: Hepatocellular Carcinoma; Hepatic Portal Vein Tumor Invasion; Tumor Thrombus

Summary: the present study aimed to assess the effectiveness of the combination treatment of atezolizumab/bevacizumab, transcatheter arterial chemoembolization (tace) and i-125 seeds brachytherapy (tace-ab-i) in patients with advanced hepatocellular carcinoma (hcc) and portal vein tumor thrombosis (pvtt). the investigators confirmed that the combination therapy yielded better survival data than the combined administration of atezolizumab/bevacizumab and tace (tace-ab) in patients with advanced hcc and type i/ii pvtt (based on cheng's pvtt classification).

this is a multicenter, open-label trial, randomized controlled to evaluate the efficacy and safety of tace-ab-i compared with tace-ab for the treatment of hcc with branch pvtt. 234 hcc patients with branch pvtt will be enrolled in this study. the patients will be treated with tace-ab-i or tace-ab using a 1:1 randomization scheme. tace will be performed for the patients after randomization. atezolizumab/bevacizumab (1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks) will be started at 3-7 days after the first tace and i-125 seeds brachytherapy and last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. for patients in the tace-ab-i arm, iodion-125 seeds will be implanted into the pvtt (according to the pre-operative planning) under ct guidance within 3-7 days after the first tace. tace and iodion-125 seeds implantation can be repeated on demand during follow-up based on the evaluation of laboratory and imaging examination.

Eligibility criteria:
inclusion criteria: * age between18 and 75 years; * has a diagnosis of hcc confirmed by radiology, histology, or cytology; * type i pvtt or type ii pvtt; * child-pugh class a; * eastern cooperative group performance status (ecog) score of 0-1; * no prior systemic therapy for hcc. * adequate hematologic and end-organ function; * at least one measurable intrahepatic target lesion. exclusion criteria: * diffuse hcc; * cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed hepatocellular/cholangiocarcinoma subtypes (confirmed by histology, or pathology) are not eligible; * evidence of extrahepatic spread (ehs); * any condition representing a contraindication to tace or i-125 seeds brachytherapy as determined by the investigators; * evidence or history of bleeding diathesis or any hemorrhage or bleeding event \>ctcae grade 3 within 4 weeks prior to randomization; * active or history of autoimmune disease or immune deficiency; * untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding; * a prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment; * evidence of bleeding diathesis or significant coagulopathy; * pregnant or breastfeeding females; * significant cardiovascular disease; * severe infection, such as active tuberculosis; * serious medical comorbidities; * history of organ or cells transplantation; * history of other uncurable malignancies.

Keywords: hepatocellular carcinoma (hcc) portal vein tumor thrombosis (pvtt) transcatheter arterial chemoembolization (tace) i-125 seeds brachytherapy atezolizumab plus bevacizumab