PRIMARY OBJECTIVES:~I. To compare Progression Free Survival (PFS) in patients with advanced HCC who receive Y90 followed by immunotherapy (atezolizumab + bevacizumab, Arm A) or Y90 followed by TKI treatment ( lenvatinib or cabozantinib, Arm B). For ARM B, [patients will receive Lenvatinib. If they have prior history of treatment with Lenvatinib, then can be given Cabozantinib]..~SECONDARY OBJECTIVES:~I. To compare the Time to Progression (TTP) in patients with advanced HCC who receive Immunotherapy combination compared to TKI following Y90.~II. To compare the Objective Response Rate (ORR) as assessed by RECIST v1.1 in patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90.~III. To compare the Duration of Response (DOR) in patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90.~IV. To compare the Clinical Benefit Rates (CBR) [CR, PR,SD] as assessed by RECIST v1.1 in patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90.~V. To compare the Overall Survival (OS) in patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90.~VI. To compare the safety and tolerability of patients with advanced HCC who receive immunotherapy combination and those who receive TKI treatment after Y90, as defined by NCI CTCAEv5.~OUTLINE:~Patients will first be treated one time with liver directed therapy, Therasphere® (Y-90), following institutional procedures. After completion of Y- 90, patients will have some recovery time (14-21 days) prior to starting systemic therapy.~Patients will be followed up for 2 years after completion of study treatment.
The purpose of this research is to compare progression free survival between two available systemic therapies - immunotherapy and tyrosine kinase inhibitors - after Therasphere® (yttrium-90) treatment in adult patients with advanced hepatocellular carcinoma. The immunotherapy consists of a standard-of-care treatment with Atezolizumab and Bevacizumab. Treatment with tyrosine kinase inhibitors consists of standard-of-care Lenvatinib or Cabozantinib.