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 |
1
Group 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.