The combination of atezolizumab and bevacizumab was recently approved by the U.S. Food and Drug Administration for the treatment of unresectable or metastatic hepatocellular carcinoma on the basis of findings from the phase III IMbrave150 trial, which showed superior overall and progression-free survival with the combination vs sorafenib. The phase IB GO30140 trial, reported in The Lancet Oncology by Lee et al, demonstrated the activity of atezolizumab plus bevacizumab in this setting and showed prolonged progression-free survival with the combination vs atezolizumab alone.
“Our study shows longer progression-free survival with a combination of atezolizumab plus bevacizumab than with atezolizumab alone in patients with unresectable hepatocellular carcinoma not previously treated with systemic therapy. Therefore, atezolizumab plus bevacizumab might become a promising treatment option for these patients.”— Lee et al
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Study Details
The multicohort trial included two cohorts of patients with unresectable hepatocellular carcinoma who had received no prior systemic treatment: in a single-group cohort, 104 patients received atezolizumab at 1,200 mg and bevacizumab at 15 mg/kg every 3 weeks; in a comparative cohort, 119 patients were randomly assigned to receive the atezolizumab/bevacizumab regimen (n = 60) or atezolizumab alone (n = 59).
The primary endpoints were objective response rate in the single-group cohort and progression-free survival in the comparative cohort, both assessed by an independent review facility using Response Evaluation Criteria in Solid Tumors version 1.1.
Key Findings
In the single-group cohort, median follow-up was 12.4 months. Objective response was observed in 37 patients (36%), with complete response observed in 12 (12%). An additional 37 patients (36%) had stable disease. Median duration of response was not reached (95% confidence interval [CI] = 11.8 months–not estimable). Median progression-free survival was 7.3 months (95% CI = 5.4–9.9 months).
In the single-group cohort, the most commonly reported grade 3 or 4 treatment-related adverse events were hypertension (13%) and proteinuria (7%). Treatment-related serious adverse events occurred in 24% of patients. Treatment-related deaths occurred in three patients (3%), with causes consisting of abnormal hepatic function, hepatic cirrhosis, and pneumonitis, respectively.
In the comparative cohort, median follow-up was 6.6 to 6.7 months. Median progression-free survival was 5.6 months (95% CI = 3.6–7.4 months) in the atezolizumab/bevacizumab group vs 3.4 months (95% CI = 1.9–5.2 months) in the atezolizumab monotherapy group (hazard ratio = 0.55, P =.011).
Objective response rates were 20% (complete response in 2%) vs 17% (complete response in 5%), with an additional 47% vs 32% of patients having stable disease. Median durations of response were not reached (95% CI = not estimable) vs not reached (95% CI = 3.7 months–not estimable).
The most commonly reported grade 3 or 4 treatment-related adverse events in the combination group were hypertension (5%) and proteinuria (3%). Treatment-related serious adverse events occurred in 12% of patients in the combination group. No treatment-related deaths were observed.
The investigators concluded, “Our study shows longer progression-free survival with a combination of atezolizumab plus bevacizumab than with atezolizumab alone in patients with unresectable hepatocellular carcinoma not previously treated with systemic therapy. Therefore, atezolizumab plus bevacizumab might become a promising treatment option for these patients.”
Kyung-Hun Lee, MD, of the Division of Hematology and Oncology, Seoul National University Hospital, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by F. Hoffmann-La Roche/Genentech. For full disclosures of the study authors, visit thelancet.com.
