IMbrave 150, atezo/bev vs sora

Background

Global, open-label, phase 3 trial in 501 patients with unresectable, systemic-treatment-naive hepatocellular carcinoma and Child-Pugh A liver function, randomized 2:1 to atezolizumab plus bevacizumab or sorafenib.

Interventions and follow up

Arm A: Atezolizumab 1200 mg + bevacizumab 15 mg/kg IV every 3 weeks
Arm B: Sorafenib 400 mg PO BID
Primary endpoint: OS and PFS (independent review, RECIST 1.1)
mFollow up: 8.6 months

Results

Death rate: 28.6% vs 39.4% (Arm A vs B); HR 0.58, 95% CI 0.42-0.79; P<.001
6-mo OS: 84.8% vs 72.2%
12-mo OS: 67.2% vs 54.6%
mPFS: 6.8mo vs 4.3mo; HR 0.59, 95% CI 0.47-0.76; P<.001

Adverse events

Overall: Grade 3-4 events 56.5% vs 55.1%; grade 5 events 4.6% vs 5.8% (Arm A vs B)
Vascular/renal: Hypertension 29.8% vs 24.4%; proteinuria 20.1% vs 7.1% (Arm A vs B)
Hepatic/constitutional: Increased AST 19.5% vs 16.7%; fatigue 20.4% vs 18.6% (Arm A vs B)
Dermatologic/GI: Pruritus 19.5% vs 9.6%; diarrhea 18.8% vs 49.4% (Arm A vs B)

Conclusions

Atezolizumab plus bevacizumab improved OS and PFS versus sorafenib in unresectable hepatocellular carcinoma, establishing a new first-line standard.

Key Limitations

Open-label design; limited to Child-Pugh A; short initial follow-up (mature OS later reported 19.2mo); upper GI endoscopy required to mitigate variceal bleeding, limiting generalizability.

Clinical Context

FDA approved atezolizumab plus bevacizumab for unresectable/metastatic HCC in May 2020; EMA approval followed. ASCO and ESMO guidelines endorse it as a preferred first-line regimen in Child-Pugh A disease without high-risk varices.

References

Finn RS et al, NEJM, 2020, PMID: 32402160
Llovet JM et al, NEJM, 2008 (SHARP), PMID: 18650514