Changes in serum tumor marker levels are efficient predictors of complete response in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Abstract Background and aims: Atezolizumab plus bevacizumab therapy is recommended as first-line regimen for unresectable hepatocellular carcinoma (uHCC). Complete response (CR) is now being experienced at a consistent rate. This study aimed to identify predictive factors for CR.Methods A retrospective analysis of 319 patients with uHCC in whom atezolizumab plus bevacizumab therapy was introduced at our and joint research institutions from October 2020 to August 2023.Results Nineteen patients (6.0%) achieved CR. Multivariate analysis identified a Child–Pugh score 5 and decrease in alpha fetoprotein (AFP) levels of more than 20% at 3 weeks as significant and independent determinants of achieving CR. Sixteen of the 19 patients (84.2%) maintained a cancer-free status. Cancer-free patients had a significantly higher proportion of lower levels of Lens culinaris agglutinin-reactive AFP isoform (AFP-L3) at CR. Patients with AFL-L3 values of 15% or higher at CR had a significantly lower duration of response (log-rank test, P = 0.032).Conclusions Changes in AFP levels are important predictors of CR achievement in atezolizumab plus bevacizumab therapy. AFP-L3 levels are important for predicting maintenance of the therapeutic response.