Following its success as a standard-of-care (SOC) frontline approach in unresectable hepatocellular carcinoma (HCC), the use of atezolizumab (Tecentriq) and bevacizumab (Avastin) has now shown improved recurrence-free survival (RFS) in the adjuvant setting. This could be a practice-changing treatment option for patients with early-stage HCC who historically have poorer prognosis, according to Ahmed O. Kaseb, MD.
The phase 3 IMBrave050 trial (NCT04102098) evaluated adjuvant atezolizumab plus bevacizumab in patients with a high risk of HCC recurrence after resection or ablation with curative intent. In a prespecified interim analysis presented during the 2023 AACR Annual Meeting, 12-month independent review facility (IRF)–assessed RFS rates increased from 65% (95% CI, 60%-71%) with active surveillance to 78% (95% CI, 73%-82%) with the immunotherapy doublet.
Although median RFS was not evaluable (NE) for both arms at a median follow-up of 17.4 months, the hazard ratio of 0.72 favored the doublet (95% CI, 0.56-0.93; P = .012). Data regarding overall survival are still immature. Regarding safety, the regimen was consistent with both the known toxicity profile of each agent and the underlying disease.
This is the first phase 3 trial to demonstrate efficacy for an adjuvant immunotherapy combination in early-stage HCC. The combination was previously approved as frontline therapy for patients with unresectable or metastatic HCC based on findings from the phase 3 IMbrave150 study (NCT03434379).
Kaseb, a professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston, emphasized the potential of this regimen to transform the treatment landscape for early-stage HCC. He highlighted the importance of the regimen's previous approval in the advanced setting as a validation of the strategy to combine a checkpoint inhibitor with anti-VEGF therapy, given HCC's dependence on VEGF-mediated angiogenesis and its immune-rich environment.
The interim efficacy and safety data from IMbrave050 presented at the meeting underscored the clinical significance of this approach in the adjuvant setting, with the potential to serve as the basis for FDA approval. This would mark the first time an adjuvant regimen is reviewed favorably by the FDA for patients with HCC.
Kaseb also discussed the future directions for immunotherapy regimens in HCC, including the exploration of combination strategies that integrate immunotherapy with targeted therapy and localized therapies, as well as investigations in the neoadjuvant setting as a preoperative treatment.
