Dr Kaseb on the Investigation of Adjuvant Atezolizumab and Bevacizumab in Early-Stage HCC

Ahmed O. Kaseb, MD, professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine,The University of Texas MD Anderson Cancer Center, discusses the significance of results from the phase 3 IMbrave050 trial (NCT04102098) of adjuvant atezolizumab (Tecentiq) and bevacizumab (Avastin) for patients with early-stage hepatocellular carcinoma (HCC).

HCC is characterized as a vascular tumor that is dependent on VEGF-mediated angiogenesis, and has an immune-rich microenvironment, Kaseb begins. However, this tumor type is also associated with a high level of PD-L1 expression. Accordingly, patients with this tumor type may benefit from an immune checkpoint inhibitor (ICI) combined with a VEGF inhibitor, Kaseb explains.

The prior FDA approval for the ICI atezolizumab and VEGF inhibitor bevacizumab in unresectable or metastatic HCC validated the benefit of this approach, and subsequently transformed the frontline treatment landscape, Kaseb continues. This approval was based on data from the phase 3 IMbrave150 study (NCT03434379).

Based on the safety and efficacy of frontline atezolizumab and bevacizumab, researchers sought to expand the regimen's indication for patients with a high risk of HCC recurrence after resection or ablation through the phase 3 IMbrave050 trial. Patients undergoing surgery typically experience an increase in the number of immune cells and VEGF expression, Kaseb says. Therefore, it was hypothesized that atezolizumab and bevacizumab may be particularly beneficial pre- or postsurgical resection in the adjuvant setting, Kaseb details.

IMbrave050 was reported to have met its primary end point in a prior press release, Kaseb reports. This outcome was expected, since the regimen's activity and safety in the frontline setting was well-established, and its performance in the adjuvant setting was thus highly anticipated, he notes.

Results from a prespecified analysis were presented at the 2023 AACR Annual Meeting and showed that the doublet increased 12-month recurrence-free survival (RFS) rates compared with active surveillance consistently across all subgroups. Moreover, the hazard ratio of 0.72 for recurrence-free survival (RFS) in the experimental and surveillance groups favored the doublet, although these data were not evaluable at the time of data cutoff. However, the overall survival analysis for this trial is still highly immature. The safety of this regimen was deemed to be in line with its known toxicity profile in the prior research.

These data will be discussed with regulatory agencies and could support the regimen's FDA approval in early-stage HCC, Kaseb says. As atezolizumab and bevacizumab are already routinely used as a frontline treatment in clinic, it will be easier to incorporate the agent into standard practice if it gains approval, Kaseb concludes.

Disclosure: Dr. Kaseb reports receiving honoraria from Roche/Genentech, Bayer, Exelixis, Eisai, Merck, Bristol-Myers Squibb, and AztraZeneca; he received grants from Roche/Genentech, Exelixis, Merck, Bristol-Myers Squibb, and AztraZeneca; he received travel funding from Roche/Genentech.