Efficacy and safety of cabozantinib for patients with advanced hepatocellular carcinoma based on albumin-bilirubin grade

Br J Cancer. 2022 Mar;126(4):569-575. doi: 10.1038/s41416-021-01532-5. Epub 2021 Oct 7.

Abstract

Background: Albumin-bilirubin (ALBI) grade is an objective measure of liver function for patients with hepatocellular carcinoma (HCC). The tyrosine kinase inhibitor cabozantinib is approved for patients with advanced HCC who have received prior sorafenib based on the phase 3 CELESTIAL trial (NCT01908426). Cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated HCC.

Methods: Patients were randomised 2:1 to receive cabozantinib 60 mg or placebo orally every day. Clinical outcomes in patients with ALBI grade 1 or 2 at baseline were evaluated in CELESTIAL. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin, with an ALBI grade of 1 defined as ≤ -2.60 score and a grade of 2 as a score of > -2.60 to ≤ -1.39.

Results: Cabozantinib improved OS and PFS versus placebo in both ALBI grade 1 (hazard ratio [HR] [95% CI]: 0.63 [0.46-0.86] and 0.42 [0.32-0.56]) and ALBI grade 2 (HR [95% CI]: 0.84 [0.66-1.06] and 0.46 [0.37-0.58]) subgroups. Adverse events were consistent with those in the overall population. Rates of grade 3/4 adverse events associated with hepatic decompensation were generally low and were more common among patients in the ALBI grade 2 subgroup.

Discussion: These results provide initial support of cabozantinib in patients with advanced HCC irrespective of ALBI grade 1 or 2.

Trial registration number: ClinicalTrials.gov number, NCT01908426.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anilides / administration & dosage*
  • Anilides / adverse effects
  • Bilirubin / analysis*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / drug therapy*
  • Female
  • Humans
  • Liver Function Tests
  • Liver Neoplasms / blood
  • Liver Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Retrospective Studies
  • Serum Albumin / analysis*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Anilides
  • Pyridines
  • Serum Albumin
  • cabozantinib
  • Bilirubin

Associated data

  • ClinicalTrials.gov/NCT01908426