No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. The phase III IMbrave050 trial results demonstrated improved recurrence-free survival with atezolizumab plus bevacizumab over active surveillance in patients with high-risk hepatocellular carcinoma after curative-intent resection or ablation. Importantly, IMbrave050 stands out as the first phase III study of adjuvant treatment for hepatocellular carcinoma to report positive results.
Liver cancer poses a significant global health challenge, ranking as the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths, according to 2020 estimates. The scale of the issue is evident, with 905,700 individuals diagnosed and 830,200 dying of liver cancer worldwide in that year alone. Moreover, estimations indicate that the number of new cases and deaths from liver cancer could rise by >55% by 2040.1 Adding to the severity of the situation is the lack of established adjuvant treatments for individuals at a high risk of hepatocellular carcinoma recurrence after curative-intent resection or ablation. To address this gap, this study focused on evaluating the efficacy of adjuvant atezolizumab plus bevacizumab in comparison to active surveillance in patients with high-risk hepatocellular carcinoma.2-4
Methods
In this active global, open-label, phase III study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four World Health Organization regions (Europe, United States, South-East Asia, and Western Pacific). Patients were randomly assigned (1:1) to receive intravenous 1,200 mg atezolizumab plus 15 mg/kg bevacizumab every three weeks for seventeen cycles (twelve months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population.2-4
Findings
The intention-to-treat population included 668 patients randomly assigned to receive either atezolizumab plus bevacizumab (n=334) or active surveillance (n=334). After a median follow-up of 17.4 months, adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (HR[95%CI]: 0.72 [CI 0.53–0.98]; p=0.012). Grade 3/4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%), two of which were treatment-related in the atezolizumab plus bevacizumab group, and one 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.2
Conclusions
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 vs. active surveillance. IMbrave050 is the first phase III 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 in more detail.2
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