Sorafenib off-target effects predict outcomes in patients treated for hepatocellular carcinoma.

Aim: Sorafenib is the standard of care in advanced hepatocellular carcinoma. This study was aimed to identify clinical parameters that may predict survival in these patients. Materials & methods: In this observational study, a training (226 patients) and validation cohorts (54 patients) were analyzed for evaluating pretreatment and on-treatment parameters. Results: At multivariate analysis, only on-treatment variables (skin toxicity, diarrhea and arterial hypertension - sorafenib off-target effects), alphafetoprotein and radiological responses predicted survival. Using the occurrence of off-target effects, a prognostic index able to distinguish three groups of patients with different survival was constructed and externally validated. Conclusion: In hepatocellular carcinoma patients, on-treatment variables are the best predictors of survival. Among these, sorafenib off-target effects may be the most useful indicators for prognostication in field practice.