Significance of post-progression therapy after tyrosine kinase inhibitors for advanced hepatocellular carcinoma

Kobe Liver Conference (KLC)

Research output: Contribution to journalArticlepeer-review


Background and Aim: Molecular-targeted therapies such as sorafenib and lenvatinib have long been used as first-line treatment for advanced hepatocellular carcinoma (aHCC). However, adverse events or limited therapeutic effects may necessitate the change to another therapeutic option, known as post-progression therapy. To investigate the significance of post-progression therapy, we analyzed the outcomes of aHCC patients following first-line molecular-targeted therapy in a real-world study. Methods: This retrospective, multicenter study involved patients with aHCC who received sorafenib or lenvatinib as first-line therapy between January 2011 and September 2021. Results: In total, 513 patients were analyzed: 309 treated with sorafenib and 204 with lenvatinib. The overall response and disease control rates were 15 and 50%, respectively, in the sorafenib group and 30 and 75%, respectively, in the lenvatinib group (P < 0.001). Kaplan–Meier analysis revealed no significant differences in progression-free survival and overall survival (OS) between the two treatments. Multivariate analysis revealed that fibrosis-4 index, disease control rate, post-progression therapy, and use of an immune checkpoint inhibitor (ICI) were significantly associated with OS. OS was significantly longer in patients who received post-progression therapy than in those who did not (log-rank P < 0.001). Most patients who received an ICI as post-progression therapy had previously received lenvatinib. Among lenvatinib-treated patients, OS was significantly longer in patients who received an ICI than in patients received another or no post-progression therapy (P = 0.004). Conclusion: The introduction of newer drugs for post-progression therapy is expected to prolong survival. ICI-based regimens appear to be effective after lenvatinib.

Original languageEnglish
Pages (from-to)427-433
Number of pages7
JournalJGH Open
Issue number6
Publication statusPublished - 2022 Jun

Bibliographical note

Funding Information:
This study was supported by Grants‐in‐Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (19K07539, 21K15950, and 21K15532). Financial support:

Publisher Copyright:
© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology


Dive into the research topics of 'Significance of post-progression therapy after tyrosine kinase inhibitors for advanced hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this