IMbrave050 Trial: Adjuvant Regimen of Atezolizumab Plus Bevacizumab in Resectable Hepatocellular Carcinoma

Get Permission

Adjuvant treatment with the combination of atezolizumab and bevacizumab achieved a statistically significant and clinically meaningful improvement in recurrence-free survival compared with active surveillance alone in patients with high-risk hepatocellular carcinoma following curative-intent resection or ablation. These findings are from a prespecified interim analysis of the phase III IMbrave050 trial, which was presented at the American Association for Cancer Research (AACR) Annual Meeting 2023.1

At a median follow-up of 17.4 months, the hazard ratio of 0.72 reflected a 28% improvement in recurrence-free survival favoring the combination (P = .012). The 12-month recurrence-free survival rate was 78% in the combination arm vs 65% in the active surveillance arm. Median recurrence-free survival was not reached in either arm.

Pierce K.H. Chow, PhD, MBBS

Pierce K.H. Chow, PhD, MBBS

“At the prespecified interim analysis, adjuvant atezolizu-mab plus bevacizumab met its primary endpoint,” said lead author Pierce K.H. Chow, PhD, MBBS, of the National Cancer Centre Singapore and Duke-NUS Medical School, Singapore. “IMbrave050 is the first phase III trial to show improvement in recurrence-free survival for hepatocellular carcinoma following resection or ablation. These results have established a benchmark in adjuvant therapy for hepatocellular carcinoma and have the potential to be practice-changing,” Dr. Chow stated at a press conference.

Commenting on the current indications for surgery and ablation in hepatocellular carcinoma, Dr. Chow explained that an efficacious adjuvant regimen “may lead to a reassessment of which patients may benefit from surgery. Currently, surgery is not offered to many patients with potentially resectable hepatocellular carcinoma with high-risk features, such as high tumor burden, poor tumor differentiation, or the presence of vascular invasion. The risk of recurrence after resection or ablation is high, up to 63% at 5 years. If the risk of recurrence is reduced by this adjuvant regimen, more patients could benefit from surgery.”

Previously, the IMbrave150 study established atezolizumab/bevacizumab as standard therapy for unresectable hepatocellular carcinoma. Up until now, there has been no standard for adjuvant therapy for resectable hepatocellular carcinoma, Dr. Chow noted.2

Study Details

The global, open-label, phase III IMbrave050 trial randomly assigned 334 patients with resectable hepatocellular carcinoma at high risk of recurrence in a 1:1 ratio to adjuvant combination therapy with atezolizumab/bevacizumab (334 patients) vs active surveillance (334 patients) over 12 months. In the experimental arm, atezolizumab was given at 1,200 mg once every 3 weeks, and bevacizumab was given at 15 mg/kg once every 3 weeks. Treatment was continued until disease recurrence or intolerable toxicity. Stratification factors included geographic region, presence and number of risk factors, and receipt of transarterial chemoembolization (TACE).

Baseline characteristics were well balanced between the two arms. Median patient age was 60, and about 83% were male. More than 80% were Asian, 11% were White, and 7% were “other” ethnicities. Most study participants (62%) had hepatitis B, and 11% had hepatitis C.

About 87% of patients in both arms had undergone resection. Most patients had one tumor (about 90%), with the longest diameter of the largest tumor at diagnosis being a median of 5.6 cm. About 11% received adjuvant TACE after resection (when indicated by local practice guidelines); 60.6% had microvascular invasion, and 41.9% had poor tumor differentiation. About 12% of patients underwent ablation. For that group, about 72% had one tumor, with the longest diameter of the largest tumor at diagnosis at a median of 2.6 cm.

Key Results

Median follow-up at data cutoff was 17.4 months. At 12 months, recurrence-free survival rate was 78% with the combination vs 65% with active surveillance. At 12 months, disease recurrence was reported in 20% of the combination arm vs 34% in the surveillance arm, a 33% difference favoring atezolizumab/bevacizumab (P = .003).

Results were consistent across all -prespecified clinical subgroups A total of 61% of the active surveillance arm crossed over to the combination therapy, as per the protocol if they had recurrence either immediately after independent facility review or after a second resection/ablation procedure.

Overall survival was immature as of the data cutoff. The median duration of treatment was about 11 months for both drugs in the combination therapy arm.


“The safety profile of adjuvant atezolizumab plus bevacizumab was generally consistent with that of each agent and with the underlying disease,” Dr. Chow noted.

At least one adverse event was reported in 98.2% of patients on the experimental arm vs 62.1% of patients on the active surveillance arm. Grade 3 or 4 adverse events occurred in 41.0% vs 13.3%, respectively. Treatment-related serious adverse events were reported in 13.3% of the combination arm. There were 27 deaths in the combination arm vs 20 in the control arm. Grade 5 toxicity occurred in six patients vs one patient, respectively, with two of the grade 5 events being related to treatment (esophageal varices hemorrhage and ischemic stroke).


For more on the use of atezolizumab plus bevacizumab in hepatocellular carcinoma from the IMbrave050 trial, see an interview with Pierce K.H. Chow, PhD, MBBS, on The ASCO Post Newsreels at

In the combination therapy arm, dose interruptions were required in 46.7%, and drug withdrawal because of toxicity occurred in 19%. Corresponding rates in the active surveillance arm were not applicable.

Closing Thoughts

During the press conference, Dr. Chow commented: “As a surgeon, I see a lot of patients come back for follow-up after surgical resection who are demoralized by the fact that there is no treatment for them to prevent recurrence. Patients with hepatocellular carcinoma [who undergo] surgical resection have such poor survival at 5 years compared with those [who have] other early-stage cancers (such as colorectal cancer), with an overall survival of 60% to 70% compared with 90%. So, this is a huge unmet clinical need for patients with hepatocellular carcinoma. I think a positive adjuvant therapy trial offers these patients hope for better survival and better cancer-free survival.” 

DISCLOSURE: The study was funded by F. Hoffmann–La Roche. Dr. Chow has served as a consultant to AUM Biosciences, BeiGene, Omega Therapeutics, Roche, IQVIA Solutions, and Sirtex; served on the speakers bureau of AstraZeneca, Bayer, Omega Therapeutics, Roche, and Worrell; has received grant/research support from Roche, Sirtex, MIRXES, Perspectum, AMILI, Stratificare; been a stockholder of Avatamed; and received honoraria from AstraZeneca, Bayer, Perspectum, Roche, Sirtex, and Worrell.


1. Chow P, Chen M, Cheng AL, et al: IMbrave050: Phase 3 study of adjuvant atezolizumab + bevacizumab versus active surveillance in patients with hepatocellular carcinoma at high risk of disease recurrence following resection or ablation. AACR Annual Meeting 2023. Abstract CT003. Presented April 16, 2023.

2. Finn RS, Qin S, Ikeda M, et al: Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382:1894-1905, 2020.

Related Articles

Expert Point of View: Stephen Lam Chan, MD

Invited discussant of the IMbrave050 trial, Stephen Lam Chan, MD, of Chinese University of Hong Kong, put the study into context. “After curative treatment, recurrence remains a big problem [in patients with hepatocellular carcinoma at high risk of disease recurrence following resection or...