Treatment of hepatocellular carcinoma: a cost analysis of yttrium-90 transarterial radioembolization versus sorafenib.

AIM: The aim was to evaluate cost-effectiveness of yttrium-90 transarterial radioembolization (TARE) in comparison to sorafenib treatment. PATIENTS & METHODS: A single-center, retrospective, observational study was performed, 166 patients with intermediate-/advanced-stage hepatocellular carcinoma were treated with sorafenib and 19 with TARE. The patients out of the sorafenib group matching the inclusion criteria for TARE, were reassigned to a subgroup SOR3. RESULTS: Mean costs for SOR3 patients amounted to €27,992 per patient, instead for TARE treatment, mean expense per patient was €17,761 (p = 0.028). Overall survival was similar between the two groups, while midterm survival rates (p = 0.012) were significantly higher with TARE treatment. CONCLUSION: TARE causes significantly lower treatment costs than sorafenib with better outcome in midterm survival.

Sorafenib prescribed by gastroenterologists and hepatologists for hepatocellular carcinoma: A retrospective, multi-institutional cohort study.

Sorafenib is the only Food and Drug Administration (FDA)-approved first-line therapy shown to have survival benefit for patients with advanced hepatocellular carcinoma (HCC). Patients with advanced HCC are often but not exclusively transferred from non-oncologists to oncologists to initiate systemic therapy. The objective of this study was to assess whether sorafenib prescribing by non-oncologists has any impact on utilization, adverse effects, cost or outcome.This was a retrospective cohort study utilizing data from patients prescribed sorafenib for HCC within Veterans Health Administration hospitals with 100% chart abstraction to confirm HCC diagnosis, identify prescribing provider specialty (oncology versus gastroenterology/hepatology), and obtain data required for cancer staging by the Barcelona Clinic Liver Cancer (BCLC) system. The primary outcome was overall survival from the time of sorafenib prescription.A total of 4903 patients who prescribed sorafenib for HCC were identified, for whom 340 patients (6.9%) were prescribed drug by a non-oncologist (Onc). BCLC Stage, age, Child-Turcotte-Pugh score, and comorbidity indices were similar between patients prescribed sorafenib by oncologists and non-oncologists. Oncologists more often discontinued sorafenib due to progression, whereas non-oncologists were more likely to continue sorafenib until death resulting in greater pill utilization and cost. Overall survival in both unadjusted and multivariable models showed no significant impact of prescriber type on survival (222 vs 217 days, P = .96), confirmed with propensity-matched subcohorts.Similar survival outcomes were observed for patients with HCC prescribed sorafenib by non-oncologists and oncologists, suggesting that non-oncologists with expertise in the management of HCC can safely and effectively administer sorafenib.

Cost-effectiveness analysis of treatment with non-curative or palliative intent for hepatocellular carcinoma in the real-world setting.

Hepatocellular carcinoma (HCC) presentation is heterogeneous necessitating a variety of therapeutic interventions with varying efficacies and associated prognoses. Poor prognostic patients often undergo non-curative palliative interventions including transarterial chemoembolization (TACE), sorafenib, chemotherapy, or purely supportive care. The decision to pursue one of many palliative interventions for HCC is complex and an economic evaluation comparing these interventions has not been done. This study evaluates the cost-effectiveness of non-curative palliative treatment strategies such as TACE alone or TACE+sorafenib, sorafenib alone, and non-sorafenib chemotherapy compared with no treatment or best supportive care (BSC) among patients diagnosed with HCC between 2007 and 2010 in a Canadian setting. Using person-level data, we estimated effectiveness in life years and quality-adjusted life years (QALYs) along with total health care costs (2013 US dollars) from the health care payer's perspective (3% annual discount). A net benefit regression approach accounting for baseline covariates with propensity score adjustment was used to calculate incremental net benefit to generate incremental cost-effectiveness ratio (ICER) and uncertainty measures. Among 1,172 identified patients diagnosed with HCC, 4.5%, 7.9%, and 5.6%, received TACE alone or TACE+sorafenib, sorafenib, and non-sorafenib chemotherapy clone, respectively. Compared with no treatment or BSC (81.9%), ICER estimates for TACE alone or TACE+sorafenib was $6,665/QALY (additional QALY: 0.47, additional cost: $3,120; 95% CI: -$18,800-$34,500/QALY). The cost-effectiveness acceptability curve demonstrated that if the relevant threshold was $50,000/QALY, TACE alone or TACE+sorafenib, non-sorafenib chemotherapy, and sorafenib alone, would have a cost-effectiveness probability of 99.7%, 46.6%, and 5.5%, respectively. Covariates associated with the incremental net benefit of treatments are age, sex, comorbidity, and cancer stage. Findings suggest that TACE with or without sorafenib is currently the most cost-effective active non-curative palliative treatment approach to HCC. Further research into new combination treatment strategies that afford the best tumor response is needed.

Cost Effectiveness of Lenvatinib, Sorafenib and Placebo in Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer.

BACKGROUND: Lenvatinib (Lenvima®) and sorafenib (Nexavar®) are the two most recently Food and Drug Administration-approved drugs for treating radioiodine-refractory differentiated thyroid cancer (RR-DTC). Both demonstrated superior progression-free survival over placebo in their respective Phase III clinical trials. This study compared the cost-effectiveness of the two treatments with placebo from a limited societal perspective. METHODS: A Markov model was developed to estimate the costs and health benefits for treatment of RR-DTC. The probabilities and survival rates were obtained from two Phase III trials: the SELECT trial comparing lenvatinib to placebo, and the DECISION trial comparing sorafenib to placebo. A bimonthly cycle length and half-cycle correction were used for a lifetime time horizon. Medical costs and utility data were obtained from RedBook, Healthcare Cost and Utilization Project, and the published literature. All costs were adjusted to US$2015, discounted at 3% annually. Then second-order Monte Carlo simulation with distributions was conducted to obtain the acceptability curve to address the uncertainty around model inputs. RESULTS: In the base case, lenvatinib was the most cost-effective treatment compared to sorafenib (incremental cost-effectiveness ratio [ICER] = $25,275/quality-adjusted life year [QALY]) and placebo (ICER = $40,869). Sorafenib is also cost-effective compared to placebo (ICER = $64,067/QALY). The treatment decisions were found to be sensitive to the treatment costs and the health utility associated with lenvatinib and its side effects. The acceptability curve showed lenvatinib optimal 80% of time at WTP of $100,000/QALY. CONCLUSIONS: This study suggests that lenvatinib is the optimally cost-effective treatment for RR-DTC, although both lenvatinib and sorafenib are cost-effective compared to placebo.

Real-World Data for the Evaluation of Transarterial Radioembolization versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis.

OBJECTIVES: To perform a cost-effectiveness analysis comparing the use of transarterial radioembolization (TARE) with that of sorafenib in the treatment of patients with intermediate or advanced hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer staging system. METHODS: Patient-level data were consecutively recorded and collected at three oncology centers in Italy. A propensity score matching was performed to compare patients with similar clinical characteristics who underwent TARE or sorafenib treatment. Clinical data from the matched cohorts were used to populate a Markov model to project, on a lifetime horizon, life years, quality-adjusted life years, and economic outcomes associated with TARE and sorafenib for both intermediate and advanced HCC stages. RESULTS: Starting from data covering 389 and 241 patients who underwent TARE and sorafenib treatment, respectively, the propensity score matching yielded a total of 308 matched patients. For intermediate-stage patients, the model estimated for TARE versus sorafenib an incremental cost-utility ratio of €3,302/QALY (incremental cost-effectiveness ratio of €1,865 per life year gained), whereas for patients in advanced stage TARE dominated (lower costs and greater health improvements) compared with sorafenib. CONCLUSIONS: From an Italian health care service perspective, TARE could be a cost-effective strategy in comparison with sorafenib for patients with intermediate or advanced HCC. The results from forthcoming randomized controlled trials comparing TARE with sorafenib will be able to confirm or reject the validity of this preliminary evaluation. In the meantime, decision makers can use these results to control and coordinate the diffusion of the technology.

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

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).

FOLFOX4 or sorafenib as the first-line treatments for advanced hepatocellular carcinoma: A cost-effectiveness analysis.

BACKGROUND: This study aimed to investigate the pharmaco-economic implications of FOLFOX4 or sorafenib for advanced hepatocellular carcinoma in China. METHODS: To conduct the analysis, we performed a Markov model to simulate the process of advanced HCC treated with sorafenib or FOLFOX4. Clinical data were obtained from the ORIENTAL trial and the EACH trial. Incremental cost-effectiveness ratio was regarded as the primary outcome in the analysis. One-way sensitivity analysis as well as probabilistic sensitivity analysis was performed to explore the impact of essential variables on the results of the analysis. RESULTS: Treatment with sorafenib provided an effectiveness gain of 0.3935 quality-adjusted life year at an average cost of $18,748.00, whereas chemotherapy of FOLFOX4 brought 0.3808 quality-adjusted life year at a cost of $6876.02. The incremental cost-effectiveness ratio of FOLFOX4 versus sorafenib was $934,801.57/QALY. In a probabilistic sensitivity analysis based on a Monte Carlo simulation of 1000 items, the probabilities of FOLFOX4 and sorafenib being cost-effective were 100% and 0% using a willingness-to-pay threshold of $20,301.00 per quality-adjusted life year. CONCLUSIONS: FOLFOX4 chemotherapy is likely to be a cost-effective option compared with sorafenib in the treatment of advanced hepatocellular carcinoma in China.

Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. METHODS: A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. RESULTS: The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO's guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. CONCLUSION: This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan.

Cost-effectiveness analysis of antiviral therapy in patients with advanced hepatitis B virus-related hepatocellular carcinoma treated with sorafenib.

BACKGROUND AND AIM: Antiviral therapy has been demonstrated to significantly improve the survival in patients with advanced hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The aim of the study was to investigate the cost-effectiveness of antiviral therapy in patients with advanced HBV-related HCC treated with sorafenib. METHODS: To conduct the analysis, a Markov model comprising three health states (progression-free survival, progressive disease, and death) was created. The efficacy data were derived from medical records. Cost data were collected based on the Chinese national drug prices. Utility data came from the previously published studies. One-way sensitivity analyses as well as probabilistic sensitivity analyses were performed to explore model uncertainties. RESULTS: In the base-case analysis, addition of antiviral therapy to sorafenib generated an effectiveness of 0.68 quality-adjusted life years (QALYs) at a cost of $25 026.04, while sorafenib monotherapy gained an effectiveness of 0.42 QALYs at a cost of $20 249.64. The incremental cost-effectiveness ratio (ICER) was $18 370.77/QALY for antiviral therapy group versus non-antiviral therapy group. On the other hand, the ICER between the two groups in patients with high or low HBV-DNA load, with or without cirrhosis, normal or elevated alanine aminotransferase/aspartate aminotransferase were $16 613.97/QALY, $19 774.16/QALY, $14 587.66/QALY, $19 873.84/QALY, $17 947.07/QALY, and $18 785.58/QALY, respectively. CONCLUSIONS: Based on the cost-effectiveness threshold ($20 301.00/QALY in China), addition of antiviral therapy to sorafenib is considered to be a cost-effective option compared with sorafenib monotherapy in patients with advanced HBV-related HCC in China from the patient's perspective.

Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment.

OBJECTIVE: To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). BACKGROUND: TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. METHODS: Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. RESULTS: API costs per kg were $347-$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128-$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. CONCLUSIONS: Mass generic production of several TKIs could achieve treatment prices in the range of $128-$4020 per person-year, versus current US prices of $75161-$139,138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients.

Cost-effectiveness analysis of axitinib through a probabilistic decision model.

INTRODUCTION: The Oncology field is characterised by a steady increase in demand and a consistent launching of innovative and expensive products. Therefore, cost-effectiveness analysis can contribute as a significant decision-making tool by elucidating the most economically efficient ways to satisfy compelling health needs. AREAS COVERED: The scope of this study is to estimate the cost-effectiveness of axitinib versus sorafenib, for the second-line treatment of renal cell carcinoma. A literature review for evidence synthesis was performed and a probabilistic Markov Model was employed to simulate disease progression. This study will also assess Value of Information. EXPERT OPINION: Compared to sorafenib, axitinib resulted in an incremental cost of 87,936 euro per quality adjusted life year. The probability of axitinib to being cost-effective at the willingness-to-pay threshold of 60,000 euro was 13%, while the corresponding probability of being cost-effective at the highest recommended willingness-to-pay threshold of 100,000 euro was 69.9%. Uncertainty was primarily attributed to the price of the product, the utility values, the progression-free survival and to a lesser degree to the overall survival. Axitinib can be considered as a cost-effective therapeutic option for second-line treatment of renal cell carcinoma.

Cost-effectiveness of sorafenib as a first-line treatment for advanced hepatocellular carcinoma.

OBJECTIVE: Sorafenib has been shown to significantly improve the overall survival of patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the cost-effectiveness of sorafenib as a first-line treatment for patients with advanced HCC. MATERIALS AND METHODS: To carry out the analysis, we collected the data on the efficacy and safety of patients treated with sorafenib from medical records and follow-up of these patients. A Markov model comprising three health states (progression-free survival, progressive disease, and death) was created to simulate the process of advanced HCC. We calculated the data on cost from the perspective of Chinese patients. Sensitivity analyses were also carried out to explore the impact of several essential variables. RESULTS: Overall, 94 patients with advanced HCC were included in our study: 70 in the Child-Pugh A group and 24 in the Child-Pugh B group. The median overall survival was 8.0 months (95% confidence interval: 7.21-8.50). In general, treatment with sorafenib was estimated to increase costs by $18,251.84 compared with best supportive care, with a gain of 0.18 quality-adjusted life years (QALYs). Thus, the incremental cost-effective ratio was $101,399.11/QALY for sorafenib versus best supportive care. In addition, in patients with Child-Pugh A liver function, the total costs and effectiveness were $20,643.06 and 0.48 QALYs, respectively, whereas in the Child-Pugh class B group, the total costs and effectiveness were $15,844.33 and 0.28 QALYs. CONCLUSION: On the basis of the commonly accepted willingness-to-pay threshold ($20,301.00/QALY in China), sorafenib is not a cost-effective option as a first-line treatment for patients with advanced HCC.

Health economic changes as a result of implementation of targeted therapy for metastatic renal cell carcinoma: national results from DARENCA study 2.

BACKGROUND: Limited data exist on the economic consequences of implementing targeted therapy (TT) for metastatic renal cell carcinoma (RCC) in a real-world setting. OBJECTIVE: To analyze health care and productivity costs for TT implementation in a national cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: Costs were measured per patient per year during a 2-yr follow-up during 2002-2005 (immunotherapy only) and 2006-2009 (TT implementation). All Danish patients with a diagnosis code for RCC and a procedure code for TT or immunotherapy were linked to the Danish National Patient Registry (contains information on all contacts with primary and secondary health sector). Health care and productivity costs were retrieved from the Danish case-mix system and Coherent Social Statistics, respectively. Drug costs were calculated separately from procedure codes and retail prices. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Generalized linear models were used to analyze costs adjusted for age, gender, and civil status. RESULTS AND LIMITATIONS: A total of 439 patients were included for 2006-2009 and 192 for 2002-2005. Comparison of the health care cost per patient per year between 2006-2009 and 2002-2005 revealed lower inpatient costs (€11 899 vs €19 944, adjusted relative risk [RR] 0.64), higher outpatient costs (€14 308 vs €6209, RR 2.39), lower radiotherapy costs (€194 vs €633, RR 0.31), higher radiology costs (€676 vs €191, RR 3.73), and higher separately calculated drug costs (€12 040 vs €3103, RR 3.82, all p<0.001) for the former. Total health care costs per patient per year did not significantly differ (€27 676 vs €27 856, RR 1.05, p=0.5) between the two periods. Income from employment did not significantly differ between 2006-2009 and 2002-2005 (RR 1.11, p=0.11) and costs associated with loss of productivity were €7852 and €8265, respectively. CONCLUSIONS: A different pattern of health care costs were observed but total health care costs per patient per year did not significantly differ after implementation of TT for patients with mRCC. PATIENT SUMMARY: In this nationwide study, we found changes in the pattern of health care costs for patients with metastatic kidney cancer after implementation of targeted therapy compared to an immunotherapy control period; however, total health care costs and income from employment were without significant changes.

Radioembolisation with yttrium‒90 microspheres versus sorafenib for treatment of advanced hepatocellular carcinoma (SARAH): study protocol for a randomised controlled trial.

BACKGROUND: Untreated advanced hepatocellular carcinoma (HCC) is linked to poor prognosis. While sorafenib is the current recommended treatment for advanced HCC, radioembolisation (RE; also called selective internal radiation therapy or SIRT) with yttrium-90 microspheres has shown efficacy in cohort studies. However, there are no head-to-head trials comparing radiation therapy with yttrium-90 microspheres and sorafenib in advanced HCC. The SARAH trial has been designed to compare the efficacy and safety of sorafenib therapy and RE using yttrium-90 resin microspheres (SIR-Spheres™; Sirtex Medical Limited, North Sydney, Australia) in patients with advanced HCC. Quality of life (QoL) and cost-effectiveness will also be compared between therapies. METHODS/DESIGN: SARAH is a prospective, randomised, controlled, open-label, multicentre trial comparing the efficacy of RE with sorafenib in the treatment of patients with advanced HCC. The trial aims to recruit adults with a life expectancy of >3 months, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, and: advanced HCC according to the Barcelona criteria (stage C) or recurrent HCC after surgical or thermoablative treatment who are not eligible for surgical resection, liver transplantation or thermal ablation; or two rounds of failed chemoembolisation. Patients will be randomised 1:1 to receive either RE or sorafenib 400 mg twice daily. All patients will be monitored for between 12 and 48 months following start of treatment. The primary endpoint of the SARAH trial is overall survival (OS). Secondary endpoints include: adverse events, progression-free survival at 6 months; tumour response rate; general or liver disease-specific QoL scores; and cost of each treatment strategy. Assuming an increase in median OS of 4 months with RE versus sorafenib therapy, randomising at least 400 patients (200 in each treatment arm) will be sufficient for 80% power and a bilateral alpha risk of 5%; therefore, 440 patients will be enrolled to allow for 10% loss of patients due to ineligibility. DISCUSSION: The SARAH trial is the first randomised head-to-head study to compare RE with sorafenib in advanced HCC, and will establish the potential role of RE in HCC treatment guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01482442, first received 28 November 2011.

Cost-effectiveness of sorafenib compared to best supportive care in second line renal cell cancer from a payer perspective in Cyprus.

The objective of this study is to assess the cost effectiveness of sorafenib as a second line treatment of advanced renal cell carcinoma compared to standard best supportive care (BSC) in Cyprus. A probabilistic Decision analytic Markov Model was created to simulate disease progression and data from landmark trials were used. Actual local costs were set according to current guidelines in Cyprus. The incremental cost per quality adjusted life year of sorafenib versus BSC was €102,059. The probability of sorafenib to be cost effective at the threshold of €60,000 was 0%. Total costs were sensitive to the price of product, its effectiveness and to a lesser degree to the utility values. Sorafenib demonstrated superior clinical effectiveness compared to BSC, but it's not cost effective under current willingness to pay threshold. Its orphan status along with solidarity principle may justify reimbursement on an individual patient basis.

Sorafenib for advanced hepatocellular carcinoma (HCC): impact of rationing in the United Kingdom.

BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) is dependent upon tumour stage, performance status (PS), severity of underlying liver disease, and the availability of appropriate therapies. The unavailability of sorafenib may have a significantly adverse effect on the prognosis of UK patients with advanced HCC. During the study period, access to sorafenib was at the discretion of local health funding bodies, a process that may delay or deny access to the drug and that remains in place for Wales, Scotland, and Northern Ireland. Here, we attempt to address the impact of this system on patients with advanced HCC in the United Kingdom. METHODS: This is a retrospective study performed in the two largest specialist hepatobiliary oncology units in the United Kingdom. Funding applications were made to local funding bodies for patients with advanced HCC for whom sorafenib was considered appropriate (advanced HCC not suitable for loco-regional therapies, compensated chronic liver disease, PS 0-2). RESULTS: A total of 133 applications were made, of which 57 (43%) were approved and 76 (57%) declined. Demographics and prognostic factors were balanced between the two groups. This cohort had a number of adverse prognostic features: patients were predominantly PS 1-2; the majority had multifocal disease with the largest lesion being >5 cm; and macroscopic vascular invasion, metastases, and AFP >,000 ng ml(-1), were each present in one-third of cases. The median time from application to funding decision was 17 days (range 3-260 days). For the primary 'intention-to-treat' analysis, median overall survival was 4.1 months when funding was declined, and 9.5 months when funding was approved (hazard ratio (HR) 0.48; 95% CI 0.3186-0.7267; P=0.0005). CONCLUSION: These data support the use of sorafenib for patients with advanced HCC as an effective intervention. In the United Kingdom, this applies to a relatively small group of patients, estimated to total ∼800 per year who, unfortunately, do not survive long enough to themselves lobby for the availability of this drug. These data provide a comparison of sorafenib with supportive care and demonstrate the potential detrimental impact on patient outcomes of rationing health-care resources on the basis of cost.