Therapeutic Efficacy and Safety of Lenvatinib after Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma

SIMPLE SUMMARY: Immune checkpoint inhibitor therapy has been rapidly developed for the treatment of unresectable hepatocellular carcinoma (HCC). In the IMbrave150 trial, atezolizumab plus bevacizumab was seen as the first-line systemic drug therapy for unresectable HCC because overall survival and progression-free survival were significantly prolonged compared with sorafenib. However, an effective regimen after atezolizumab plus bevacizumab failure has not yet been established. Lenvatinib, on the other hand, also demonstrated good outcomes in unresectable HCC in the REFLECT trial as first-line therapy and is currently positioned as one of the second-line therapies after atezolizumab plus bevacizumab. The aim of this retrospective study was to evaluate the efficacy and safety of lenvatinib after atezolizumab plus bevacizumab for unresectable HCC. ABSTRACT: A total of 137 HCC patients treated with atezolizumab plus bevacizumab from October 2020 to September 2022 were enrolled. The median overall survival (OS) and progression-free survival (PFS) from the beginning of atezolizumab plus bevacizumab were 21.1 months (range, 18.8 months–not reached) and 10.5 months (range, 8.2–12.1 months), respectively. Fifty patients were diagnosed with progressive disease after atezolizumab plus bevacizumab. Of this group, 24 patients were administered lenvatinib, and the median OS and PFS from the beginning of lenvatinib were 15.3 months (range, 10.5 months–not reached) and 4.0 months (range, 2.5–6.4 months), respectively. The objective response rates based on the response evaluation criteria in solid tumors (RECISTs) criteria version 1.1 and modified RECISTs were 33.3% and 54.2%, respectively. There was no significant difference in the median serum alpha-fetoprotein level between before and after lenvatinib. In the multivariate analysis, Child–Pugh class A (hazard ratio 0.02, 95% confidence interval (CI) 0.02–0.76, p = 0.02) and intrahepatic tumor occupancy rate < 50% (hazard ratio < 0.01, 95% CI 0.003–0.35, p < 0.01) were the significant factors for OS. There were some frequent adverse events (AEs) in patients treated with lenvatinib such as hypertension, fatigue, anorexia, proteinuria, and so on, but none directly caused death. In conclusion, lenvatinib after atezolizumab plus bevacizumab for unresectable HCC should be considered an effective treatment option.