Mac-2 binding protein glycosylation isomer predicts tolerability and clinical outcome of lenvatinib therapy for hepatocellular carcinoma

J Hepatobiliary Pancreat Sci. 2021 Jun;28(6):498-507. doi: 10.1002/jhbp.954. Epub 2021 Apr 17.

Abstract

Background: Many patients with hepatocellular carcinoma present with impaired hepatic function, which often requires interruption or withdrawal of lenvatinib due to associated adverse events. We aimed to identify pre-treatment predictors of tolerability and clinical outcome of lenvatinib therapy.

Methods: Eighty patients who received lenvatinib at our institution between 2018 and 2020 were included in this study. We assessed essential factors associated with prolonged progression-free survival (PFS), using Cox proportional hazards model. We also investigated the correlation between the factor identified as contributing most to PFS and the relative dose intensity (RDI), response rate, and duration of treatment with lenvatinib.

Results: Pre-treatment level of Mac-2-binding protein glycosylation isomer (M2BPGi) showed significant association with PFS (hazard ratio = 0.52, P = .0358). Low M2BPGi levels (<1.5) correlated significantly with longer PFS than higher levels (P = .0003). Patients with M2BPGi <1.5 achieved significantly higher RDI, objective response rate, and disease control rate, and maintained lenvatinib treatment for longer than those with baseline values ≥1.5. Patients with M2BPGi ≥1.5 had a higher incidence of adverse events such as fatigue and anorexia.

Conclusions: Baseline M2BPGi levels may predict the tolerability and treatment response to lenvatinib. Patients with high M2BPGi levels may less likely to benefit from lenvatinib therapy.

Keywords: Mac-2 binding protein glycosylation isomer; hepatocellular carcinoma; lenvatinib; molecular targeted therapy; tolerability.

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Glycosylation
  • Humans
  • Liver Neoplasms* / drug therapy
  • Phenylurea Compounds / adverse effects
  • Quinolines

Substances

  • Phenylurea Compounds
  • Quinolines
  • lenvatinib