Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients

Int J Cancer. 2016 Aug 15;139(4):928-37. doi: 10.1002/ijc.30124.

Abstract

The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE-S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4-13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE-S in future randomized controlled trials.

Keywords: biomarker; dermatologic adverse events; hepatocellular carcinoma; sorafenib; transarterial chemoembolization.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / therapy*
  • Chemoembolization, Therapeutic* / adverse effects
  • Chemoembolization, Therapeutic* / methods
  • Disease Progression
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / etiology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Niacinamide / administration & dosage
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / adverse effects
  • Prognosis
  • Retrospective Studies
  • Sorafenib
  • Treatment Outcome
  • Young Adult

Substances

  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib