Cost-Effectiveness of Cabozantinib in the Second-Line Treatment of Advanced Hepatocellular Carcinoma.

BACKGROUND: Treatment options are limited for patients with advanced hepatocellular carcinoma (HCC) that progresses after treatment with sorafenib. Cabozantinib, an oral small molecule inhibitor of multiple tyrosine kinase receptors, recently showed improved overall survival (OS) compared with placebo in sorafenib-pretreated patients with advanced HCC in the CELESTIAL trial. This study assessed the cost-effectiveness of cabozantinib for second-line treatment of patients with advanced HCC from a US healthcare system perspective. PATIENTS AND METHODS: Cost and utility data were extracted from the CELESTIAL trial and used to determine the cost-effectiveness of cabozantinib compared with placebo plus best supportive care. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) gained by using cabozantinib compared with placebo plus best supportive care in sorafenib-pretreated HCC. RESULTS: In the base-case analysis using data from the CELESTIAL trial, the incremental QALY and ICER were 0.067 and $1,040,675 for cabozantinib compared with placebo and best supportive care. OS reported in the CELESTIAL trial (hazard ratio, 0.76; 95% CI, 0.63-0.92) had the strongest association with the ICER. In one-way sensitivity analyses, there were no scenarios in which cabozantinib was cost-effective. In a cost-threshold analysis, cabozantinib would have to be priced at least $50 per pill to be cost-effective considering a willingness to pay of $100,000 per QALY. Although the CELESTIAL trial demonstrated that cabozantinib improves OS compared with placebo in patients with HCC that progresses after treatment with sorafenib, our analysis shows that cabozantinib is not a cost-effective therapy in this scenario. CONCLUSIONS: At current costs, cabozantinib is not cost-effective for second-line therapy of HCC in the United States.

Insurance status impacts treatment for hepatocellular carcinoma.

INTRODUCTION AND AIM: Previous studies have identified treatment disparities in the treatment of hepatocellular carcinoma (HCC) based on insurance status and provider. Recent studies have shown more Americans have healthcare insurance; therefore we aim to determine if treatment disparities based on insurance providers continue to exist. MATERIALS AND METHODS: A retrospective database analysis using the NIS was performed between 2010 and 2013 including adult patients with a primary diagnosis of HCC determined by ICD-9 codes. Multivariable logistic regressions were performed to analyze differences in treatment, mortality, features of decompensation, and metastatic disease based on the patient's primary payer. RESULTS: This study included 62,368 patients. Medicare represented 44% of the total patients followed by private insurance (27%), Medicaid (19%), and other payers (10%). Patients with Medicare, Medicaid, and other payer were less likely to undergo liver transplantation [(OR 0.63, 95% CI 0.47-0.84), (OR 0.23, 95% CI 0.15-0.33), (OR 0.26, 95% CI 0.15-0.45)] and surgical resection [(OR 0.74, 95% CI 0.63-0.87), (OR 0.40, 95% CI 0.32-0.51), (OR 0.42, 95% CI 0.32-0.54)] than patients with private insurance. Medicaid patients were less likely to undergo ablation then patients with private insurance (OR 0.52, 95% CI 0.40-0.68). Patients with other forms of insurance were less likely to undergo transarterial chemoembolization (TACE) compared to private insurance (OR 0.64, 95% CI 0.43-0.96). CONCLUSION: Insurance status impacts treatment for HCC. Patients with private insurance are more likely to undergo curative therapies of liver transplantation and surgical resection compared to patients with government funded insurance.

Independent Predictors of Mortality and Resource Utilization in Viral Hepatitis Related Hepatocellular Carcinoma.

INTRODUCTION: Hepatitis B (HBV) and C viruses (HCV) are important causes of hepatocellular carcinoma (HCC). Our aim was to assess mortality and resource utilization of patients with HCC-related to HBV and HCV. MATERIAL AND METHODS: National Cancer Institute's Surveillance, Epidemiology and End Results (SEER)-Medicare linked database (2001-2009) was used. Medicare claims included patient demographic information, diagnoses, treatment, procedures, ICD-9 codes, service dates, payments, coverage status, survival data, carrier claims, and Medicare Provider Analysis and Review (MEDPAR) data. HCC related to HBV/HCV and non-cancer controls with HBV/HCV were included. Pair-wise comparisons were made by t-tests and chi-square tests. Logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals (CIs) were used. RESULTS: We included 2,711 cases of HCC (518 HBV, 2,193 HCV-related) and 5,130 non-cancer controls (1,321 HBV, 3,809 HCV). Between 2001-2009, HCC cases related to HBV and HCV increased. Compared to controls, HBV and HCV patients with HCC were older, more likely to be male (73.2% vs 48.9% and 57.1% vs. 50.5%), die within one-year (49.3% vs. 20.3% and 52.2% vs. 19.2%), have decompensated cirrhosis (44.8% vs. 6.9% and 53.9% vs. 10.4%) and have higher inpatient ($60.471 vs. $47.223 and $56.033 vs. $41.005) and outpatient charges ($3,840 vs. $3,328 and $3,251 vs. $2,096) (all P < 0.05). In two separate multivariate analyses, independent predictors of one-year mortality were older age, being male and the presence of decompensated cirrhosis. CONCLUSIONS: The rate of viral hepatitis-related HCC is increasing. Mortality and resource utilization related to HBV and HCV-related HCC is substantial.

Economic growth leads to increase of obesity and associated hepatocellular carcinoma in developing countries.

 Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer related death worldwide. In recent years, the prevalence of HCC has increased in both developing and developed countries. Most HCC cases develop in the presence of advanced chronic liver disease related to viral hepatitis. In particular hepatitis B virus and hepatitis C virus infections are considered as major HCC risk factors worldwide. However, current studies provide strong evidence for increasing numbers of HCC in nonalcoholic fatty liver disease (NAFLD). NAFLD represents the hepatic manifestation of metabolic syndrome which is based on obesity and insulin resistance. Epidemiologic data clearly demonstrates that NAFLD and obesity-related disorders are significant risk factors for tumor development in general and HCC in particular. As a consequence of life style changes towards higher calorie intake and less exercise, obesity and metabolic syndrome are spreading all over the world. Due to this increase in obesity and metabolic syndrome NAFLD-related HCC will become a major health care problem in the future. In conclusion, better understanding of the impact of NAFLD and obesity in the development of HCC will improve our treatment strategies of HCC and allow preventive measures.

Cost-effectiveness of whole-body bone scans in the pre-liver transplant assessment of patients with hepatocellular carcinoma in Southern Brazil.

BACKGROUND: Bone metastases (BM) are rare in patients with early-stage hepatocellular carcinoma (HCC). In many centers, liver transplantation (LTx) policies require patients with HCC to undergo bone scans (BSs). METHODS: We retrospectively assessed the benefit of BS for patients with a diagnosis of HCC wait-listed for LTx. RESULTS: BS was performed in 259 of 328 patients (78.9%) and was suggestive of BM in only one (0.4%). At follow-up, 276 patients had received LTx, of whom 207 had undergone BS. Histopathological examination of explants failed to confirm the presence of HCC in 20 patients from the BS group. The survival and recurrence rates of the 187 patients with confirmed HCC in the explant who underwent BS as part of pre-LTx assessment and 69 patients who did not undergo BS were compared. The one- and five-yr post-transplant survival rates were 81% and 69%, respectively, in the BS group vs. 78% and 62%, respectively, in patients who did not undergo BS (p = 0.25). The one- and five-yr post-LTx recurrence rates were 4.8% and 10.7%, respectively, in the BS group vs. 2.9% and 10.1%, respectively, in patients who did not undergo BS (p = 0.46). CONCLUSIONS: BS generated expenditures of US$39 296 and was not cost-effective.

In whom, how and how often is surveillance for hepatocellular carcinoma cost-effective?

BACKGROUND: Despite well known worldwide differences in hepatocellular carcinoma incidence, which reflect different risk profiles, current recommendation of surveillance with ultrasound and alpha-fetoprotein twice-a-year has been restricted to cirrhotic patients. To evaluate the generalizability of this recommendation, we reviewed the clinical charts of hepatocellular carcinoma cases in a Mexican scenario. To evaluate efficiency, we performed a literature based cost-effectiveness analysis. METHODS: Charts pertaining to 174 consecutive patients with histologically proven hepatocellular carcinoma, seen at a tertiary health care centre were analysed. A decision tree, based on the surveillance and recall algorithm of the European Association for the Study of the Liver was constructed. Ultrasound and/or alpha-fetoprotein, performed every six or twelve months were the diagnostic alternatives, and accurate diagnoses, direct medical costs and cost-effectiveness ratios were the outcomes of interest. RESULTS: Male:female ratio was 1.2:1, underlying liver disease was secondary to alcohol in 44% and to hepatitis C virus in 26%, documented cirrhosis was present in 42%. Cost-effectiveness ratios for twice-a-year ultrasound and alpha-fetoprotein ranged from $303.09 to $346.22 U.S. dollars per accurate diagnosis, and for annual ultrasound from $115.86 to $116.42 U.S. dollars. CONCLUSIONS: Male gender, hepatitis C and cirrhosis were not predominant characteristics in our series. If a hepatocellular carcinoma surveillance program were to be instituted in our setting, or where patient characteristics are similar to ours, it probably should not be restricted to cirrhotic patients. Recommended performance of ultrasound and alpha-fetoprotein every six months is the least cost-effective surveillance strategy. Instead, annual ultrasound optimises diagnoses and costs.