Effectiveness of Sorafenib Dose Modifications on Treatment Outcome of Hepatocellular Carcinoma: Analysis in Real‐Life Settings

Controlling adverse events through dose reduction can enhance drug adherence and treatment response. Currently, there is no guide for sorafenib dosing. The aim of this study was to evaluate whether sorafenib dosing could affect treatment outcomes. A total of 782 hepatocellular carcinoma (HCC) patients treated with sorafenib were evaluated for sorafenib dosing and its modifications via medical records at baseline and regular followed-up. Study outcomes included progression-free survival (PFS), overall survival (OS), sorafenib duration, cumulative dose, adverse events (AEs), and drug discontinuation. The median patient survival was 7.7 months. Overall, 242 (30.9%) patients underwent dose reduction and 121 (17.5%) discontinued sorafenib due to AEs. In multivariate analysis, dose reduction was identified to be independently predictive of PFS and OS. The 800-to-400 mg/d group provided significantly better PFS than the 800 mg/d-maintained group or the 800-to-600 mg/d group. Likewise, the 800-to-400 mg/d group resulted in a significantly better OS than other dosing. However, dose reduction to 200 mg/d led to significantly worse PFS and OS. Hand-foot skin reaction and drug discontinuation due to AEs were higher in the 800-to-600 mg/d group than the 800-to-400 mg/d group. The 800-to-400 mg/d group had significantly longer treatment duration and higher cumulative dose than the 800 mg/d-maintained group. Sorafenib dose reduction can improve HCC survival and increase patient tolerance and adherence coupled with longer duration and higher cumulative dose. Dose reduction from 800 mg/d to 400 mg/d than to 600 mg/d is recommended when clinically warranted. However, dose reduction to 200 mg/d is not recommendable.