Survival and cost‐effectiveness of sorafenib therapy in advanced hepatocellular carcinoma: An analysis of the SEER–Medicare database

Abstract

Sorafenib is the only chemotherapeutic approved for treatment of advanced hepatocellular carcinoma (HCC). However, its effectiveness in patients with Child‐Pugh class B cirrhosis and any moderating effects of health system characteristics are unclear. We examined the survival and cost‐effectiveness associated with sorafenib in elderly patients with advanced HCC. We performed an analysis of Medicare beneficiaries with HCC diagnoses from 2007 to 2009. We compared advanced stage patients with HCC (American Joint Committee on Cancer stage III/IV) who received sorafenib within 6 months of diagnosis (and were otherwise untreated) to advanced stage patients with HCC who received no therapy (control). We performed univariate and multivariate analyses to identify predictors of survival. Incremental cost‐effectiveness ratios (ICERs) were calculated for sorafenib‐treated and control patients. We included 228 sorafenib‐treated patients and 870 control patients. The median survival of the sorafenib‐treated patients was 150.5 days versus 62 days for control patients. On multivariate analysis, significant predictors of improved survival were treatment with sorafenib (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.57‐0.77), being seen at a National Cancer Institute–designated cancer center (HR, 0.77; 95% CI, 0.62‐0.97), and being seen at a transplantation center (HR, 0.77; 95% CI, 0.65‐0.93). Predictors of worse survival included stage IV disease (HR, 1.40; 95% CI, 1.24‐1.58), decompensated cirrhosis (HR, 1.49; 95% CI, 1.30‐1.70), and treatment in an urban setting (HR, 1.45; 95% CI, 1.21‐1.73.) Although sorafenib use was associated with a survival benefit (HR, 0.61; 95% CI, 0.47‐0.79) among patients with decompensated cirrhosis, the median survival benefit was 31 days, and it was not cost‐effective (ICER, $224,914 per life year gained). Conclusion: Sorafenib is associated with improved survival in elderly patients with advanced HCC; however, it is not cost‐effective among those with hepatic decompensation. (Hepatology 2017;65:122‐133).

No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma

“…Second, most patients present with various adverse events of sorafenib, with drug-related grade 3 or 4 adverse events, according to the National Institute of Health’s Common Terminology Criteria for Adverse Events version 3.0, observed in 37.4% of Japanese patients participating in the GIDEON study [4]. Finally, as sorafenib treatment is expensive, its associated cost represents a limitation [5]. Although several studies have investigated predictive biomarkers of sorafenib efficacy, there have been no established predictive biomarkers [6-9].…”

RAB10 overexpression promotes tumor growth and indicates poor prognosis of hepatocellular carcinoma

“…Drugs designed against a specific target of certain cancers will affect the cancer nidus and kill cancer cells without harming neighboring non-cancerous cells [7–9]. For instance, sorafenib is a molecular-targeted agent for the treatment of HCC with Child-Pugh A liver function [10–12]. It is a multi-kinase inhibitor of tumor growth and angiogenesis, which can significantly inhibit C and B-Raf serine/ threonine kinases, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, tyrosine kinases and FLT-3 (fms related tyrosine kinase 3) [12–14].…”

“…For instance, sorafenib is a molecular-targeted agent for the treatment of HCC with Child-Pugh A liver function [10–12]. It is a multi-kinase inhibitor of tumor growth and angiogenesis, which can significantly inhibit C and B-Raf serine/ threonine kinases, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, tyrosine kinases and FLT-3 (fms related tyrosine kinase 3) [12–14]. At present, very few molecular-targeted agents have been approved for the treatment of HCC.…”

Evolving role of Sorafenib in the management of hepatocellular carcinoma

“…A study published in 2017 analysing the SEER-Medicare database, reported that elderly patients with advanced stage HCC may survive longer if treated with Sorafenib vs placebo (150.5 d vs 62 d, respectively), while the most remarkable factor associated with increased mortality was treatment taking place in an urban setting, although this survival effect was found to be neither prolonged, nor cost-effective in decompensated patients[31]. Currently, a randomized controlled phase 3 study - the B Child Patient-Optimization of Sorafenib Treatment (BOOST) study - is ongoing so as to evaluate the safety and efficacy of Sorafenib in CP B patients and is going to provide helpful information regarding the treatment of patients with decompensated disease[32].…”