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Copyright ©The Author(s) 2021.
World J Hepatol. Sep 27, 2021; 13(9): 1132-1142
Published online Sep 27, 2021. doi: 10.4254/wjh.v13.i9.1132
Table 1 Results of phase Ib GO30140 study
Arm A
Arm F
Atezolizumab and bevacizumab combination (n = 104), median follow up 12.4 mo
Atezolizumab and bevacizumab combination (n = 60), median follow up 6.6 mo
Atezolizumab monotherapy (n = 59), median follow up 6.7 mo
ORR, n (%)37 (36)12 (20)10 (17)
CR, n (%)12 (12)1 (2)3 (5)
DCR, n (%)78 (75)40 (67)29 (49)
Median PFS, mo7.4 (5.6-10.7)5.6 (3.6-2.4)3.4 (1.9-5.2)
HR (80%CI)-0.55 (0.40-0.74), P value (0.0108)
12 mo PFS (%)38
12 mo OS (%)63
Table 2 Results of IMBrave 150 trial
Results
Atezolizumab and bevacizumab arm
Sorafenib arm
Statistically significant
Estimated OS at 6 mo (%)84.872.2
Estimated OS at 12 mo (%)67.254.6
PFS (mo)6.84.3HR for progression or death was 0.59 (0.47-0.76) P < 0.0001
Confirmed ORR as per independent mRECIST assessment (%)27.311.9
As per HCC specific mRECIST CR (%)5.5-
Disease Control Rate (ORR + SD) (%)73.655.3
Table 3 Grade 5 events in both the arms IMBrave 150 trial
Atezolizumab and bevacizumab (n = 15), grade 5 adverse events
Sorafenib (n = 9), grade 5 adverse events
Gastrointestinal Haemorrhage (3)Death (2)
Pneumonia (2)Hepatic cirrhosis (2)
Empyema, gastric ulcer perforation, abnormal hepatic function, liver injury, multi-organ dysfunction syndrome, esophageal varices haemorrhage, subarachnoid haemorrhage, respiratory distress, sepsis and cardiac arrest (1 in each patient)Cardiac arrest, cardiac failure, general physical health deterioration, hepatitis E, peritoneal haemorrhage (1 in each patient)
Table 4 Advanced hepatocellular carcinoma in special subset of population with absolute and relative contraindication for atezolizumab and bevacizumab combination
Special population
Absolute contraindication for atezolizumab and bevacizumab combination
Relative contraindication for atezolizumab and bevacizumab combination
Comments
Solid organ transplantationYesN/AIf HCC in patients with liver transplant, transplant rejection can be potentially lethal. Sorafenib or lenvatinib are preferred first line options
HIV patientsN/ANo dataThis was an exclusion criteria in IMBrave150 trial. The NCT04487067 AMETHISTA study of atezolizumab and bevacizumab in HCC is including patients with HIV disease who are stable on HAART, with CD4+T cell count ≥ 200/µL, and an undetectable viral load
Prior or active autoimmune disease (AID)Yes, in patients when AID including autoimmune hepatitis, reactivation can be life threatening, neurological or neuromuscular disorders, poorly controlled AID on high dose immunosuppressionCan be used after discussion with patients and care givers about risk and benefit if do not fall in subgroups described in absolute contraindicationsPatients with symptomatic AID are at higher risk for flare. Sorafenib or lenvatinib are preferred first line options in such patients
Inflammatory bowel diseaseBevacizumab can increase complication risk in patients with Crohn’s disease with fistulaCan be used after discussion with patients and care givers about risk and benefit in patients with quiescent diseaseSelective immunosuppressants like vedolizumab may be better before considering the ICP therapy
Significant cardiovascular/thromboembolic diseaseN/ABevacizumab increases risk of HTN, thromboembolic and cardiovascular eventsCan be used after discussion with patients and care givers and treating hypertension
HaemodialysisN/ANo data available, can be considered after discussing risk and benefit and limited evidenceA recent study of 55 patients with metastatic RCC on haemodialysis showed relative safety of sorafenib, nivolumab and atezolizumab in small subgroup of patients[33]