GALNT14 genotype-guided chemoembolization plus sorafenib therapy in hepatocellular carcinoma: a randomized trial

Wei Ting Chen, Shi Ming Lin, Wei Chen Lee, Ting Jung Wu, Chen Chun Lin, Chien Heng Shen, Ming Ling Chang, Chih Lang Lin, Chau Ting Yeh*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations

Abstract

Background: GALNT14-rs9679162 “TT” genotype is associated with favorable clinical outcomes in hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We investigated whether patients with GALNT14-rs9679162 “non-TT” unfavorable genotype benefited from chemoembolization plus sorafenib combination therapy. Methods: Intermediate stage HCC patients were recruited for GALNT14-rs9679162 genotyping before TACE. Patients with “TT” genotype received only TACE, labeled as TT (TACE) group. Patients with “non-TT” genotype (“GG” or “GT”) were randomized to receive either TACE alone, labeled as Non-TT (TACE) group, or TACE plus sorafenib, labeled as Non-TT (TACE + Sora) group. The latter group received sorafenib 400 mg daily plus TACE. Results: From October 2015 to April 2019, 103 HCC patients scheduled to receive chemoembolization were screened. Of them, 84 met inclusion criteria and were assigned to TT (TACE) (n = 25), Non-TT (TACE) (n = 30) and Non-TT (TACE + Sora) (n = 29) groups according to their GALNT14 genotypes. Repeated TACE sessions were performed on-demand and patients were followed until November 2020. It was found that TT (TACE) and Non-TT (TACE + Sora) patients had shorter time-to-complete response compared with that in Non-TT (TACE) patients (p < 0.001 and 0.009, respectively). These two groups also had longer time-to-TACE progression (p < 0.001 and 0.006, respectively) and longer progression-free survival (p = 0.001 and 0.021, respectively). However, TT (TACE) patients harbored longer overall survival compared with those in non-TT (TACE + Sora) and non-TT (TACE) patients (p = 0.028, < 0.001, respectively). Conclusion: Combination of sorafenib and TACE for “non-TT” patients partially overcame the genetic disadvantage on treatment outcomes in terms of time-to-complete response, time-to-TACE progression and progression-free survival. Trial registration: ClinicalTrials.gov NCT02504983. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)148-158
Number of pages11
JournalHepatology International
Volume16
Issue number1
DOIs
StatePublished - 02 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022, Asian Pacific Association for the Study of the Liver.

Keywords

  • Angiogenesis
  • Barcelona clinic liver cancer stage
  • Biomarker
  • Complete response
  • Liver cancer
  • Overall survival
  • Polypeptide N-acetylgalactosaminyltransferase 14
  • Progression-free survival
  • Single-nucleotide polymorphism
  • Targeted drug

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