Liver and Bile
Lancet. 2023;402(10415):1835–47
Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): A randomized, open-label, multicenter, phase 3 trial
Background: No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. The aim of this study was to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma.
Methods: In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centers in 26 countries in 4 WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary end point was recurrence-free survival by independent review facility assessment in the intention-to-treat population.
Findings: The intention-to-treat population included 668 patients randomly assigned between December 31, 2019, and November 25, 2021, to either atezolizumab plus bevacizumab (n = 334) or to active surveillance (n = 334). At the prespecified interim analysis (October 21, 2022), median duration of follow-up was 17.4 months (interquartile range, 13.9–22.1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE] [95% confidence interval {CI}: 22.1–NE]) compared with active surveillance (median, NE [95% CI: 21.4–NE]; hazard ratio = 0.72 [adjusted 95% CI: 0.53–0.98]; p = 0.012). Grade 3 or 4 adverse events occurred in 136 of 332 patients (41%) who received atezolizumab plus bevacizumab and 44 of 330 patients (13%) in the active surveillance group. Grade 5 adverse events occurred in 6 patients (2%, 2 of which were treatment related) in the atezolizumab plus bevacizumab group, and 1 patient (< 1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab.
Interpretation: Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To the authors’ knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully.