Early diarrhoea under sorafenib as a marker to consider the early migration to second-line drugs

United European Gastroenterol J. 2021 Jul;9(6):655-661. doi: 10.1002/ueg2.12111. Epub 2021 Jul 6.

Abstract

Background: Despite atezolizumab and bevacizumab (A + B) is currently the first-line treatment for hepatocellular carcinoma (HCC) patients, some patients will not be adequate for this combination. In the setting of sorafenib some adverse events have been proposed as prognostic factors.

Objective: To characterize the early diarrhoea development as prognostic factor in 344 HCC patients.

Methods: The development of early diarrhoea in sorafenib treatment defined as patients who developed diarrhoea and needed dose modification within the first 60 days of treatment (e-diarrhoea) and 3-grouping variables were analysed: Patients with e-diarrhoea, patients who developed diarrhoea after the first 60 days of treatment (L-diarrhoea) and patients that never developed diarrhoea (never diarrhoea).

Results: The median overall survival in sorafenib treated patients was significantly different across groups (6.8 months for e-diarrhoea, 26.7 months for L-diarrhoea and 13.3 months for never-diarrhoea). The emergence of e-diarrhoea was associated with poor outcomes (hazard ratio [HR] 1.84 [95%CI 1.15-2.95]), while there was no increased/decreased risk of dismal evolution in patients with L-diarrhoea (HR 0.66 [95%CI 0.42-1.03]).

Conclusion: The emergence of e-diarrhoea in HCC patients treated with sorafenib is an early predictor of dismal evolution under this therapy. Thus, prompt identification of these non-responders may be useful for an early switch to second-line therapies.

Keywords: diarrhoea; hepatocellular carcinoma; resistance; sorafenib; survival; tyrosine kinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Diarrhea / chemically induced*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Liver Neoplasms / complications
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Sorafenib
  • Survival Rate
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Sorafenib