Effectiveness and safety of Atezolizumab and Bevacizumab as conversion therapy for unresectable or advanced HCC in real-world clinical practice in Russia: Multicenter retrospective observational study

Introduction. Hepatocellular carcinoma (HCC) is a rare disorder in Russia, but its 1-year mortality rate is comparable to that of pancreatic cancer, reflecting its high aggressiveness and poor prognosis. Atezolizumab combined with Bevacizumab (A + B) is the standard of care for hepatocellular carcinoma (HCC) with a high objective response rate (ORR).

Aim. To evaluate the potential of systemic immunotargeted therapy (ITT) with a combination of A+B to downstage advanced HCC and convert nonsurgical candidates into eligible candidates for transplant, i.e. the state that meets the criteria for orthotopic liver transplantation (OLT), and to explore the safety after ITT.

Materials and methods. A real-world retrospective study to evaluate the efficacy of A+B therapy in converting patients with advanced HCC to a state amenable to surgical treatment and outcomes of OLT was conducted. The results of 12 patients with BCLC-B3 and C hepatocellular carcinoma who received A + B therapy at standard doses from January 1, 2019, to May 2024 at the Russian cancer center and the transplant center were presented. The effectiveness of therapy, the median number of ITT cycles administered, changes in the alpha-fetoprotein (AFP) levels, the safety profile, and progression-free survival (PFS) and overall survival (OS) rates were assessed.

Results. The median number of ITT cycles administered was 8. The median waiting period for OLT after completion of ITT was up to 2 months. The median alpha-fetoprotein (AFP) level decreased from 1975 to 8.2 ng/mL. A complete response was observed in 1 case (8.3%), HCC stage was downstaged to Milan Criteria in 2 cases (16.7%), and to University of California, San Francisco (UCSF) Criteria in 3 cases (25%). The results demonstrated 1-, 3-, and 5-year overall survival rates of 91.7%, 73%, and 73%, respectively. The mortality rate was 33.3%, or 4 out of 12 cases, with 2 of these deaths not being associated with tumor progression.

Conclusion. In our retrospective study, A + B systemic therapy demonstrated high efficacy and safety and may represent a promising treatment option for conversion therapy of inoperable HCC.

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