Drug |
Sorafenib |
Lenvatinib |
Atezolizumab + Bevacizumab |
Drug class |
Multi-kinase inhibitor targeting VEGFR 2-3, PDGFR, and RAF kinase |
Multi-kinase inhibitor targeting VEGFR 1-3, PDGFR, FGFR 1-4, KIT, and RET |
Atezo: Immune checkpoint inhibitor, anti-PD-L1 Beva: anti-VEGF |
Eligible patients |
Patients with advanced stage HCC ineligible/after progression to surgical or locoregional therapies, Child Pugh A, ECOG PS 0-2, with no prior systemic therapy |
Patients with unresectable HCC, BCLC B or C, Child Pugh A, ECOG PS 0-1 with no prior systemic therapy. Ps: excluded patients with >50% liver involvement, invasion of the bile duct, or invasion of the main portal vein |
Patients with locally advanced or metastatic and/or unresectable HCC, with no prior systemic therapy. Child Pugh A, ECOG PS 0-1 |
Overall survival (months) (95%CI) |
Drug: 10.7 (9.4-13.3) |
Lenvatinib: 13.6 (12.1-14.9) |
Atezo + Beva: 19.2 (17-23.7) |
|
Placebo: 7.9 (6.8-9.1) |
Sorafenib: 12.3 (10.4-13.9) |
Sorafenib: 13.4 (11.4-16.9) |
|
HR: 0.69 (0.55-0.87), P<0.0001 |
HR: 0.92 (0.79-1.06) |
HR: 0.66 (0.52-0.85), P=0.0009 |
PFS/TTP (months) |
Drug: 5.5 (4.1-6.9) |
Lenvatinib: 7.4 (6.9-8.8) |
Atezo + Beva: 6.9 (5.7-8.6) |
|
Placebo: 2.8 (2.7-3.9) |
Sorafenib: 3.7 (3.6-4.6) |
Sorafenib: 4.3 (4-5.6) |
|
HR: 0.58 (0.45-0.74), P<0.0001 |
HR: 0.66 (0.57-0.77), P<0.0001 |
HR: 0.65 (0.53-0.81), P=0.0001 |
Overall response rate - RECIST (%) |
Sorafenib: ORR: 2% CR: 0% PR:2% SD:71% DCR:43% |
Lenvatinib: ORR: 18.8% CR: <1% PR: 18% SD: 54% PD: 18% DCR: 72.8% |
Atezo + Beva: ORR: 30% CR: 8% PR: 22% SD: 44% DCR: 74% PD: 19% |
|
|
Sorafenib: ORR: 6.5% |
Sorafenib: ORR: 11% |
|
|
CR: < 1% PR: 6% SD: 53% PD: 32% DCR: 59% |
CR: <1% PR: 11% SD: 43% DCR: 55% PD: 25% |
Overall response rate - mRECIST (%) |
NA |
Lenvatinib: ORR: 24.1% CR: 1% PR: 23% SD: 51% PD: 15% DCR: 75.5% |
Atezo + Beva: ORR: 35% CR: 12% PR: 23% SD: 37% DCR: 73% PD: 20% |
|
|
Sorafenib: ORR: 9.2% CR: <1% PR: 9% SD: 51% PD: 31% DCR: 60.5% |
Sorafenib: ORR: 14% CR: 3% PR: 11% SD: 41% DCR: 55% PD: 25% |
Adverse events, any grade |
Diarrhea (39%), fatigue (22%), HFSR (21%), anorexia (14%), hypertension (5%), bleeding (7%) |
Hypertension (42%), diarrhea (39%), anorexia (34%), decreased weight (31%), fatigue (30%), HFSR (27%), proteinuria (25%) |
Hypertension (29.8%), fatigue (20.4%), proteinuria (20.1%), pruritus (19.5%), AST increase (19.5%), diarrhea (18.8%), anorexia (17.6%) |
Adverse events grade 3 or 4 |
HFSR (8%), diarrhea (8%), fatigue (4%), hypertension (2%), bleeding (1%) |
Hypertension (23%), decreased weight (8%), anorexia (5%), diarrhea (4%), fatigue (4%), HFSR (3%) |
Hypertension (15.2%), AST increase (7%), ALT increase (3.6%), proteinuria (3%); |
Dose schedule and route of administration |
400 mg of sorafenib (two |
≥60 kg: 12 mg/day (three 4-mg tablets taken orally once a day) |
Intravenous infusion of 1200 mg atezolizumab + 15 mg/kg |
|
200-mg tablets) taken orally twice daily |
<60 kg: 8 mg/day (two 4-mg tablets taken orally once a day) |
bevacizumab every 3 weeks |
Approved for HCC |
Europe, USA, Brazil |
Europe, USA, Brazil |
Europe, USA, Brazil |