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

Table 3 Summary of the efficacy and safety findings

Ref.	Finn et al[12], 2020		Lee et al[16], 2020
Schemes	Atezolizumab-bevacizumab combination therapy	Sorafenib monotherapy	Atezolizumab-bevacizumab combination therapy given in both Arm A and F		Atezolizumab monotherapy
Total patients			Group A	Group F+
	n = 336	n = 165	n = 104	n = 60	n = 59
Primary efficacy outcomes
Mortality
n (%)	96 (28.6)	65 (39.4)	16 (27)	0 (0)	18 (31)
Two-tail P value	P = 0.0033	P = 0.0033	No P value reported	No P value reported	No P value reported
HR for disease progression, CI	0.59, 95%CI: 0.47-0.76	Not applicable	NA	NA	NA
Two-tail P value	P < 0.001
HR for death, CI	0.58, 95%CI: 0.42-0.79	NA	NA	NA	NA
Two-tail P value	P < 0.001
HR for progression-free survival, CI	NA	NA	0.55, 80%CI: 0.40-0.74		NA
Two-tail P value			P = 0.011
Secondary efficacy outcomes tumor survival and progression of disease
Overall/survival rate, n (%)	n not explicitly reported	n not explicitly reported	57 (55)	16 (27)	18 (31)
n (%)	-67.2	-54.6
95%CI			CI not reported	CI not reported	CI not reported
	61.3-73.1	45.2-64
Median overall survival in mo	Not estimable	13.2 mo	17.1 mo	Median overall survival was not reached	Median overall survival was not reached
95%CI
		(10.4 to not estimable)	(13.8 to not estimable)	(8.3 to not estimable)	(8.2 to not estimable)
6 mo overall survival rates			NA	NA	NA
95%CI	84.80%	72.20%
	80.9-88.7	80.9-88.7
12 mo overall survival rates	67.20%	54.60%	NA	NA	NA
95%CI	61.3-73.1	45.2-64
Median progression-free survival (mo), (95%CI)	6.8 mo	4.3 mo	7.3 mo	5.6 mo	3.4 mo
	(5.7-8.3)	(4.0-5.6)	(5.4-9.9)	(3.6-7.4)	(1.9-5.2)
Overall confirmed objective response				n not explicitly reported (20%)	n not explicitly reported (17%)
n (%) as per RECIST 1.1				(11-32)	(8-29)
95%CI	89 (27.3%)	19 (11.9%)	37 (36%)
	(22.5-32.5)	(7.4-18)	(26-46)
Confirmed objective response-complete response as per RECIST 1.1, n (%)	18 (5.5)	0 (0)	12 (12)	1 (2)	3 (5)
Confirmed objective response-Partial response as per RECIST 1.1, n (%)	71 (21.8)	19 (11.9)	25 (24)	11 (18)	7 (12)
Stable disease n (%) as per RECIST 1.1	151 (46.3)	69 (43.4)	37 (36)	28 (47)	19 (32)
Progressive disease
n (%) as per RECIST 1.1	64 (19.6)	39 (24.5)	25 (24)	17 (28)	25 (42)
Disease control rate, n (%)	240 (73.6)	88 (55.3)	74 (71)	40 (67)	29 (49)
Ongoing objective response at data cut off, n (%)	77/89 (86.5)	13/19 (68.4)	NA	NA	NA
Safety outcomes (adverse events)
Overall patients with an adverse event from any cause, n (%)	323 (98.2)	154 (98.7)	100 (96)	57 (95)	52 (90)
Treatment-related serious adverse events, n (%)	125 (38)	48 (30.8)	25 (24)	7 (12)	2 (3)
Treatment-related mortality	161 deaths (%)		3 (3%)	0 (%)	NA
	It was not explicitly stated how many deaths there were in relation to treatment in either intervention or control arm1
Adverse events leading to dose modifications, n (%)	163 (49.5)	95 (60.9)	50 (48)	9 (15)	5 (9)
Adverse events leading to withdrawal from any trial drug, n (%)	51 (15.5)	16 (10.3)	18 (17)	6 (10)	0 (0)
Number of participants with Grade 3 and above, n (%)	5-15 (4.6)	9 (5.8)	55 (53)	22 (37)	8 (14)
Types of Grade 3-4 adverse events
Adverse events	Note: All stratified data reported below are Grade 3 or 4		Note: All stratified data reported below are Grade 3, except increased aspartate aminotransferase (note stratification)
Hypertension, n (%)	50 (15.2)	19 (12.2)	15 (14)	3 (5)	1 (1)
Decreased appetite, n (%)	4 (1.2)	6 (3.8)	1 (1)	0 (0)	0 (0)
Fatigue, n (%)	8 (2.4)	5 (3.2)	1 (1)	0 (0)	0 (0)
Pyrexia, n (%)	4 (1.2)	2 (1.3)	2 (2)	0 (0)	0 (0)
Rash, n (%)	0 (0)	4 (2.6)	0 (0)	0 (0)	0 (0)
Diarrhea, n (%)	6 (1.8)	8 (5.1)	3 (3)	1 (2)	0 (0)
Abdominal pain, n (%)	4 (1.2)	4 (2.6)	4 (4)	0 (0)	0 (0)
Constipation, n (%)	0 (0)	0 (0)	1 (1)	0 (0)	0 (0)
Cough, n (%)	0 (0)	1 (0.6)	0 (0)	0 (0)	0 (0)
Nausea, n (%)	1 (0.3)	1 (0.6)	NA	NA	NA
Weight decrease, n (%)	0 (0)	1 (0.6)	NA	NA	NA
Epistaxis, n (%)	0 (0)	1 (0.6)	NA	NA	NA
Asthenia, n (%)	1 (0.3)	4 (2.6)	NA	NA	NA
Infusion-related reaction, n (%)	8 (2.4)	0 (0)	NA	NA	NA
Palmar-Plantar erythrodysesthesia syndrome, n (%)	0 (0)	13 (8.3)	NA	NA	NA
Proteinuria, n (%)	10 (3)	1 (0.6)	7 (7)	3 (5)	0 (0)
Increased aspartate aminotransferase, n (%)	23 (7.0)	8 (5.1)	Grade 3: 3 (3)	2 (3)	2 (3)
			Grade 4: 2 (2)
Increased alanine aminotransferase, n (%)	12 (3.6)	2 (1.3)	NA	NA	NA
Blood bilirubin increase, n (%)	8 (2.4)	10 (6.4)	NA	NA	NA
Decreased platelet count, n (%)	11 (3.3)	2 (1.3)	5 (5)	0 (0)	0 (0)
Pancreatitis, n (%)	1 (0.3)	2 (1.3)	NA	NA	NA
Hepatic Encephalopathy, n (%)	2 (0.6)	2 (1.3)	NA	NA	NA
Pulmonary Embolism, n (%)	3 (0.9)	2 (1.3)	NA	NA	NA
Cholangitis, n (%)	4 (1.2)	1 (0.6)	NA	NA	NA
Acute kidney failure, n (%)	1 (0.3)	3 (1.9)	NA	NA	NA
Gastrointestinal hemorrhage, n (%)	4 (1.2)	3 (1.9)	NA	NA	NA
Esophageal varices hemorrhage, n (%)	6 (1.8)	1 (0.6)	NA	NA	NA
Upper gastrointestinal hemorrhage, n (%)	2 (0.6)	2 (1.3)	NA	NA	NA
Asthenia, n (%)	1 (0.3)	4 (2.6)	NA	NA	NA
Types of Grade 5 adverse events
Grade 5 adverse events, n (%)	15 (4.6)	9 (5.8)	0 (0)	0 (0)	0 (0)
	Not stratified1	Not stratified1
Not evaluable/data missing
Not evaluable, n (%)	8 (2.5)	14 (8.8)	NA	NA	NA
Data missing, n (%)	14 (4.3)	18 (11.3)	NA	NA	NA

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; CI: Confidence interval; HR: Hazard ratio; NA: Not available.