Atezolizumab plus bevacizumab versus sorafenib or atezolizumab alone for unresectable hepatocellular carcinoma: A systematic review

Table 1 Characteristics of the two ongoing and two completed clinical trials

Ongoing clinical trials	La Roche[14], 2020	Hack et al[15], 2020
Country of enrollment	Italy	170 sites in 25 countries (Asia)
Study design	Single-arm, multi-Center, randomized clinical control trial	Multi-center randomized open-label, clinical control trial
Study phase	IIIb	III
Study quality	NA (study is still ongoing)	NA (study is still ongoing)
Intervention	Atezolizumab plus bevacizumab	Atezolizumab plus bevacizumab
	Dose: atezolizumab 1200 mg IV infusion q3w + bevacizumab 15 mg/kg IV Q3W	Dose: atezolizumab 1200 mg every 3 wk + bevacizumab 15 mg/every 3 wk
Control	Standard of care	Active surveillance
	No specifications for control arm reported
Number of patients	150	662
Intervention/control	Intervention not specified	Intervention 501
	Control: Not specified	Control: 119
Median age (range)	Not reported	Not reported
Intervention/control	Study included individuals > 18 yr	Study included individuals > 18 yr
-Duration of follow-up in mo	Not reported	Intervention: 8.6 mo
Intervention/control		Control: 6.5 mo
Types of outcomes reported	Overall survival	Overall survival
	Median progression-free survival	Median progression-free survival
	Grade 3-5 adverse events	Grade 3 or 4 adverse events
	Disease control	Disease control
	Objective response rate
	Time to progression
	Duration of response
	Post-progression survival
Data that could not be evaluated/data missing	NA (study is still ongoing)	NA (study is still ongoing)
Completed studies	Finn et al[12], 2020	Lee et al[16], 2020
Country/ies of Enrollment	111 sites in 17 countries, which include the United States, China, Japan, Germany, France, South Korea, Russia, Canada, and Taiwan	26 sites in 7 countries, which include the United States, Japan, South Korea, Taiwan, Australia, and New Zealand
Study design	Open-label, randomized clinical trial	Multi-arm study with five cohorts
		However, only the two cohorts focusing on hepatocellular carcinoma, Groups A and F, are described here in this study
Phase	III	Ib
Study Quality	Low risk of bias	Low risk of bias
Intervention	Atezolizumab plus bevacizumab	Atezolizumab plus bevacizumab
	Dose: 1200 mg atezolizumab + 15 mg/kg of bevacizumab IV q3w	Dose: 1200 mg atezolizumab + 15 mg/kg of bevacizumab IV q3w
Control	Sorafenib monotherapy	Atezolizumab monotherapy
	Dose: 400 mg sorafenib PO BID	Dose: 1200 mg atezolizumab
Number of patients	501	403
Intervention/control	Intervention: 336	Group A1: 104
	Control: 165	Group F+: 60
		Control:
		59 included in efficacy analysis1
		58 included in safety analysis
		1 discontinued before receiving any treatment due to elevated alkaline phosphatase concentrations1
Median duration of follow-up (mo, [IQR])	Overall: 8.6 mo	Overall follow-up not given, see stratified data below
Intervention/control		Group A1: 12.4 (IQR 8.0-16.2)
	Intervention: 8.9	Group F+: 6.6 (IQR 5.5-8.5)
		Control: 6.7 (IQR 4.2-8.2)
	Control: 8.1
Primary outcomes reported	Mortality rates	Mortality rates
	Hazard ratio for death	Hazard ratio for death
Secondary Outcomes reported	Overall survival	Overall survival
	Median progression free survival	Median progression free survival
	Grade 3-5 adverse events	Grade 3-4 adverse events
	Disease control	Disease control
	Objective response rate	Objective response rate
	Time to progression	Time to progression
	Duration of response	Duration of response
	Post-progression survival	Post-progression survival

¹Group A: Patients with hepatitis B virus DNA of 500 IU/mL or less and ongoing anti-hepatitis B virus treatment for at least 3 mo before and at study entry; patients enrolled in Group F must have had hepatitis B virus DNA of 500 IU/mL or less measured up to 28 d before study entry and anti-hepatitis B virus treatment for at least 14 d before study entry. +: Group F: Patients in Child-Pugh class A, life expectancy of 3 mo and platelet count or > 75000/μL. NA: Not applicable.