title: Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma.
abstract: Phase III trials show sorafenib improves survival in advanced hepatocellular carcinoma (HCC). Because of narrow trial eligibility, results may not be generalizable to a broader HCC population. We sought to evaluate the effectiveness of initial sorafenib versus no treatment among Medicare beneficiaries with advanced HCC.
  
  
  
  Patients with advanced HCC diagnosed from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Eligible patients received initial sorafenib or no therapy and were covered by Medicare parts A, B, and D. Sorafenib use and outcomes were described in this population. Using a propensity score (PS)-matched sample, we compared the effectiveness of sorafenib versus no treatment by Cox proportional hazards and binomial regression, using a landmark requiring all patients to survive ≥60 days after diagnosis.
  
  
  
  Of 1,532 patients, 27% received initial sorafenib. Median duration of sorafenib use was 60 days (interquartile range [IQR], 30-107 days), and median survival from first prescription was 3 months (IQR, 1-8 months). In the PS-matched cohort, median survival was 3 months from the 60-day landmark in sorafenib-treated (n = 223) and 2 months in untreated (n = 223) patients (adjusted hazard ratio, 0.95 [95% confidence interval (CI), 0.78-1.16]). Sorafenib was associated with a nonsignificant reduction in mortality at 3 months (44% versus 51%; adjusted risk ratio, 0.88 [95% CI, 0.72-1.07]), but no reduction thereafter.
  
  
  
  Survival after sorafenib initiation in newly diagnosed Medicare beneficiaries with HCC is exceptionally short, suggesting trial results are not generalizable to all HCC patients. The downsides of sorafenib use-high drug-related symptom burden and high drug cost-must be considered in light of this minimal benefit.
  
  
  
  The findings of a median survival of only 3 months in Medicare beneficiaries with HCC prescribed sorafenib as first-line therapy highlight the questionable value of sorafenib in this population. Patients should be cautioned that outside of the narrow confines of randomized trials, their life expectancy may be very short, and any benefit of sorafenib is likely to be quite small. Given that sorafenib causes considerable adverse effects and offers no symptom palliation, supportive care should be discussed as a reasonable alternative to sorafenib, particularly for patients who have a poor performance status or advanced cirrhosis.
authors.affiliation: University of North Carolina Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA Division of Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina, USA hanna_sanoff@med.unc.edu.
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Sanoff
authors.affiliation: University of North Carolina Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: YunKyung
authors.initials: Y
authors.lastname: Chang
authors.affiliation: University of North Carolina Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA Department of Epidemiology, Center for Pharmacoepidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Lund
authors.affiliation: Indiana University Simon Cancer Center, Indianapolis, Indiana, USA.
authors.forename: Bert H
authors.initials: BH
authors.lastname: O'Neil
authors.affiliation: University of North Carolina Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA Division of Pharmaceutical Outcomes and Policy, University of North Carolina Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA Department of Health Policy and Management, University of North Carolina Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Stacie B
authors.initials: SB
authors.lastname: Dusetzina
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D016527:Drug Costs; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Aged; Carcinoma, hepatocellular; Drug costs; Liver diseases; Liver neoplasms; Medicare; Sorafenib