Send to

Choose Destination
Aliment Pharmacol Ther. 2019 Mar;49(5):482-491. doi: 10.1111/apt.15088. Epub 2019 Jan 29.

Systematic review with meta-analysis: the critical role of dermatological events in patients with hepatocellular carcinoma treated with sorafenib.

Author information

Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad de Barcelona, Barcelona, Spain.
Medical Statistics Core Facility, IDIBAPS, Hospital Clinic Barcelona & Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Hospital Clinic, Barcelona, Spain.
Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.



The positive results of the REFLECT trial in terms of survival (sorafenib vs lenvatinib) offer a new first-line option for hepatocellular carcinoma. Additionally, the expected results of immunotherapy could change the first-line treatment in hepatocellular carcinoma or the clinical trial design in first and second-line.


To evaluate the impact of dermatologic adverse events under sorafenib in hepatocellular carcinoma patients as a clinical marker to predict prognosis and critically evaluate outcomes within trials.


A systematic search of original articles published until October 2018 was performed using PubMed/MEDLINE and a meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.


A total of 393 studies were identified and 13 articles with 2035 patients (79.5% Child-Pugh-A, 73.2% BCLC-C) were selected for qualitative and quantitative analysis. The main type of dermatologic adverse events was hand-foot skin reaction (47.7%) but other dermatologic adverse events were reported in 31.7% of the cases. Presence of dermatologic adverse events was associated with a lower mortality when compared with those patients without them (pooled Hazard Ratio for the univariate analysis 0.45 (95% CI: 0.38-0.53) and there was no heterogeneity for the analysis (P = 0.511; I2  = 0.0%). Refuting this association would require the future report of 1370 negative studies.


This meta-analysis shows a clinically meaningful association between dermatologic adverse events and a higher probability of longer survival. These data support the use of dermatologic adverse events in the clinical decision-making when informing the prognosis and when systemic treatment is decided.


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center