Comparing the impact of atezolizumab plus bevacizumab and lenvatinib on the liver function in hepatocellular carcinoma patients: A mixed-effects regression model approach

Cancer Med. 2023 Dec;12(24):21680-21693. doi: 10.1002/cam4.6726. Epub 2023 Nov 21.

Abstract

Aim: This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma.

Methods: We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity-score-matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed-effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow-up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups.

Results: Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were -2.41 ± 0.40 and -2.44 ± 0.42 at baseline, and -2.17 ± 0.56 and -2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p < 0.001), there was no significant difference in the rate of ALBI score deterioration between the groups (p = 0.06). Subgroup analyses showed that LEN-treated patients with BCLC advanced stage (p = 0.02) and those who initially received the full dose (p < 0.001) had a significantly greater worsening of ALBI score compared to Atez/Bev.

Conclusions: Using a nonlinear mixed-effects regression approach, which allowed for the inclusion of cases with treatment interruption, we found no significant difference in the trend of liver function deterioration between the Atez/Bev and LEN groups. Caution should be exercised for LEN-treated patients with BCLC advanced stage or those receiving the full dose of LEN.

Keywords: ALBI score; atezolizumab plus bevacizumab; lenvatinib; liver function; mixed-effects regression model.

MeSH terms

  • Bevacizumab / adverse effects
  • Carcinoma, Hepatocellular* / drug therapy
  • Humans
  • Liver Neoplasms* / drug therapy
  • Retrospective Studies

Substances

  • lenvatinib
  • Bevacizumab
  • atezolizumab