Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma
Journal
New England Journal of Medicine
Journal Volume
382
Journal Issue
20
Pages
1894-1905
Date Issued
2020
Author(s)
Finn R.S.
Qin S.
Ikeda M.
Galle P.R.
Ducreux M.
Kim T.-Y.
Kudo M.
Breder V.
Merle P.
Kaseb A.O.
Li D.
Verret W.
Xu D.-Z.
Hernandez S.
Liu J.
Huang C.
Mulla S.
Wang Y.
Lim H.Y.
Zhu A.X.
IMbrave150 Investigators
Abstract
BACKGROUND The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma. METHODS In a global, openlabel, phase 3 trial, patients with unresectable hepatocellular carcinoma who had not previously received systemic treatment were randomly assigned in a 2:1 ratio to receive either atezolizumab plus bevacizumab or sorafenib until unacceptable toxic effects occurred or there was a loss of clinical benefit. The coprimary end points were overall survival and progressionfree survival in the intentiontotreat population, as assessed at an independent review facility according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). RESULTS The intentiontotreat population included 336 patients in the atezolizumab–bevacizumab group and 165 patients in the sorafenib group. At the time of the primary analysis (August 29, 2019), the hazard ratio for death with atezolizumab–bevacizumab as compared with sorafenib was 0.58 (95% confidence interval [CI], 0.42 to 0.79; P<0.001). Overall survival at 12 months was 67.2% (95% CI, 61.3 to 73.1) with atezolizumab–bevacizumab and 54.6% (95% CI, 45.2 to 64.0) with sorafenib. Median progressionfree survival was 6.8 months (95% CI, 5.7 to 8.3) and 4.3 months (95% CI, 4.0 to 5.6) in the respective groups (hazard ratio for disease progression or death, 0.59; 95% CI, 0.47 to 0.76; P<0.001). Grade 3 or 4 adverse events occurred in 56.5% of 329 patients who received at least one dose of atezolizumab–bevacizumab and in 55.1% of 156 patients who received at least one dose of sorafenib. Grade 3 or 4 hypertension occurred in 15.2% of patients in the atezolizumab–bevacizumab group; however, other highgrade toxic effects were infrequent. CONCLUSIONS In patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progressionfree survival outcomes than sorafenib. Copyright ? 2020 Massachusetts Medical Society.
SDGs
Other Subjects
atezolizumab; bevacizumab; sorafenib; antineoplastic agent; atezolizumab; bevacizumab; monoclonal antibody; programmed death 1 receptor; abdominal pain; adult; aged; alopecia; Article; asthenia; body weight loss; cancer combination chemotherapy; cancer patient; cancer survival; confidence interval; constipation; controlled study; coughing; decreased appetite; diarrhea; disease course; drug efficacy; drug eruption; drug fatality; drug fever; drug safety; drug withdrawal; empyema; epistaxis; esophagus hemorrhage; esophagus varices; fatigue; female; gastrointestinal hemorrhage; hand foot syndrome; hazard ratio; heart arrest; heart failure; hemoperitoneum; hepatitis E; human; hyperbilirubinemia; hypertension; hypertransaminasemia; infusion related reaction; injection site reaction; intention to treat analysis; liver cell carcinoma; liver cirrhosis; liver dysfunction; liver injury; major clinical study; male; multicenter study; multiple organ failure; nausea; overall survival; phase 3 clinical trial; pneumonia; priority journal; progression free survival; proteinuria; pruritus; randomized controlled trial; respiratory distress; response evaluation criteria in solid tumors; sepsis; side effect; stomach perforation; subarachnoid hemorrhage; thrombocytopenia; treatment response; clinical trial; Kaplan Meier method; liver cell carcinoma; liver tumor; middle aged; quality of life; survival analysis; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Hepatocellular; Female; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Programmed Cell Death 1 Receptor; Quality of Life; Survival Analysis
Publisher
Massachussetts Medical Society
Type
journal article