scholarly journals Sorafenib for the treatment of advanced hepatocellular carcinoma

2010 ◽  
Vol 14 (Suppl 1) ◽  
pp. 17-21
Author(s):  
M Connock ◽  
J Round ◽  
S Bayliss ◽  
S Tubeuf ◽  
W Greenheld ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cost Effectiveness ◽  
Decision Problem ◽  
Best Supportive Care ◽  
Base Case ◽  
Advanced Hepatocellular Carcinoma ◽  
Patient Access ◽  
Advanced Hcc ◽  
Patient Access Scheme ◽  
Access Scheme

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of sorafenib according to its licensed indication for advanced hepatocellular carcinoma (HCC). The ERG report was based on the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The licensed indication for sorafenib specifies advanced HCC patients for whom locoregional intervention and surgery are unsuitable or had been unsuccessful. The clinical evidence came from a multicentre randomised controlled trial (Study of Heart and Renal Protection; SHARP) of sorafenib plus best supportive care versus placebo plus best supportive care, with 602 participants of a predominantly European ethnicity broadly comparable to the UK population. The submitted evidence indicated that for advanced HCC patients with Child–Pugh grade A liver function and relatively good Eastern Cooperative Oncology Group performance status, sorafenib on average improves overall survival by 83 days relative to placebo, and also increases time-to-radiological disease progression. Sorafenib therapy had little or no effect on time-to-symptom progression or on quality of life as measured using a disease-specific questionnaire. Sorafenib treatment was associated with increased incidence of hypertension and of gastrointestinal and dermatological problems. However, the therapy was reasonably well tolerated and, in SHARP, withdrawals from treatment due to adverse events were similar in the sorafenib and placebo arms, although more temporary reductions in dose were required in the sorafenib than in the placebo group. In the base case, the manufacturer’s submitted economic analysis generated a deterministic incremental cost-effectiveness ratio (ICER) of £64,754 per quality-adjusted life-year (QALY). The ERG extracted individual patient data for overall survival and disease progression, reran the economic model to check the submitted cost-effectiveness results, and performed new analyses which the ERG considered relevant to the decision problem; these analyses delivered ICERs between £76,000/QALY and £86,000/QALY. The guidance issued by NICE (7 May 2009) stated that sorafenib, within its licensed indication, is not recommended for the treatment of advanced (Barcelona-Clínic Liver Cancer stage C) HCC patients for whom surgical or locoregional therapies have failed or are not suitable, and people currently receiving sorafenib for the treatment of HCC should have the option to continue treatment until they and their clinician consider it appropriate to stop. Subsequently the manufacturer submitted a patient access scheme to the Department of Health. The base-case ICER submitted by the manufacturer for this scheme was £51,899/QALY. When the ERG reran the model with inputs considered relevant to the decision problem the ICER estimates ranged between £53,000 to £58,000/QALY and substantially higher values depending on the nature of the sensitivity analyses. NICE considered the impact of the patient access scheme and determined that it was not sufficient to alter the guidance.

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

2019 ◽  
Vol 17 (6) ◽  
pp. 669-675 ◽  
Author(s):  
Enrique Soto-Perez-de-Celis ◽  
Pedro N. Aguiar ◽  
Mónica L. Cordón ◽  
Yanin Chavarri-Guerra ◽  
Gilberto de Lima Lopes
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cost Effectiveness ◽  
Supportive Care ◽  
Cost Effective ◽  
Best Supportive Care ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
Advanced Hcc ◽  
The Cost

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.

Cost-effectiveness of atezolizumab and bevacizumab in advanced hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18829-e18829
Author(s):  
Kishan Patel ◽  
Stacey Stein ◽  
Janki Luther ◽  
Scott F. Huntington
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cost Effectiveness ◽  
Willingness To Pay ◽  
Incremental Cost ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Health State ◽  
Advanced Hepatocellular Carcinoma ◽  
Lifetime Horizon ◽  
Advanced Hcc

e18829 Background: The IMbrave150 trial found that atezolizumab and bevacizumab significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with locally advanced metastatic or unresectable hepatocellular carcinoma (HCC), compared to sorafenib. However, atezolizumab and bevacizumab are costly treatments and are administered indefinitely until disease progression. Therefore, it is unclear whether atezolizumab-bevacizumab is cost-effective in this clinical setting. Methods: We constructed a partitioned survival model to compare the costs and effectiveness of atezolizumab-bevacizumab to sorafenib in advanced HCC. PFS and OS curves for each treatment strategy were derived from the IMbrave150 trial using parametric survival modeling. The utility of each health state and the costs of treatment, adverse events, and terminal care were derived from literature and Medicare fee schedules. We calculated the incremental cost-effectiveness ratio (ICER) of atezolizumab-bevacizumab from a US healthcare perspective, using a lifetime horizon, an annual discount rate of 3%, and a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of model conclusions. Results: Atezolizumab-bevacizumab was associated with an incremental cost of $102,648 and an incremental effectiveness of 0.42 QALYs compared to sorafenib, leading to an ICER of $244,213/QALY (Table). The price of atezolizumab would need to be reduced by 40% (from ̃$9,400 to ̃$5,700 per dose) or the price of bevacizumab would need to be reduced by 47% (from ̃$8,400 to ̃$4,400 per dose) for atezolizumab-bevacizumab to be cost-effective compared to sorafenib. Alternatively, the price of both atezolizumab and bevacizumab would need to be simultaneously decreased by ̃21% for the combination therapy to be cost-effective. Our model was most sensitive to the hazard ratios (HR) of OS and PFS; varying the HRs across the 95% confidence interval reported in IMbrave150 (0.42-0.79) corresponded to ICERs of $137,435/QALY and $621,365/QALY, respectively. During probabilistic sensitivity analyses, >99%, 99%, and 90% of iterations produced ICERs greater than willingness-to-pay thresholds of $50,000/QALY, $100,000/QALY, and $150,000/QALY, respectively. Conclusions: Use of atezolizumab-bevacizumab for advanced HCC is unlikely to be cost-effective under current pricing. Significant price reduction of atezolizumab and/or bevacizumab would be required to reduce the ICER to a more widely acceptable value.[Table: see text]

scholarly journals Isolated Right Ventricular Metastasis in a Woman with Advanced Hepatocellular Carcinoma after Palliative Therapy

2019 ◽  
Vol 13 (3) ◽  
pp. 487-497
Author(s):  
Chun-Ting Fan ◽  
Wei-Wen Lin ◽  
Ming-Jer Chen ◽  
Sz-Iuan Shiu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Literature Review ◽  
Supportive Care ◽  
Right Ventricular ◽  
Palliative Therapy ◽  
Best Supportive Care ◽  
Optimal Treatment ◽  
Cardiac Metastasis ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

Hepatocellular carcinoma (HCC) with cardiac metastasis represents a group of rarity and poor prognosis. Few case reports have described this patient entity, and it remains unclear regarding the optimal treatment and predicted outcome for these patients. In our case, we represented a 67-year-old female patient with presentations of dyspnea and heart murmur, which conducted to the diagnosis of advanced HCC with isolated right ventricular metastasis. Because of multiple comorbidities regarding cardiac and pulmonary systems, she received best supportive care and survived 2 months after initial diagnosis. A systemic literature review of 80 published cases (including our patient) since the 1950s was also performed from PubMed, and the data were gathered from the medical record and literature reviews. In our review, patients with advanced HCC and cardiac metastasis involved the right heart mainly with a predominance of right atrium (53%). Meanwhile the overall 3-month survival rate in our review was 70.7%. In subgroup analysis, the overall 3-month survival was highest (97%) in patients treated with surgery and other therapies, and lowest (27%) in patients with best supportive care. To our knowledge, this is the first comprehensive literature review addressing the epidemiology, optimal treatment, and prognosis for advanced-stage HCC with cardiac metastasis. We suggest that abnormal cardiac murmur in patients with history of HCC should prompt investigation for tumor involvement of the heart. We also emphasize individualized treatment as well as prognostic measurement accordingly.

scholarly journals Cabozantinib for patients with advanced hepatocellular carcinoma: a cost-effectiveness analysis

2019 ◽  
Vol 12 ◽  
pp. 175628481987830 ◽  
Author(s):  
Amir Shlomai ◽  
Moshe Leshno ◽  
Daniel A. Goldstein
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cost Effectiveness ◽  
Incremental Cost ◽  
Systemic Therapy ◽  
Kinase Inhibitor ◽  
Controlled Trial ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Life Years ◽  
Prior Systemic Therapy

Background and aims: The multi-kinase inhibitor sorafenib is a first-line drug for patients with advanced hepatocellular carcinoma (HCC). Treatment options for patients whose disease has progressed on sorafenib are limited. In a recent randomized controlled trial (CELESTIAL trial), patients with advanced HCC who had failed prior systemic therapy had moderate progression-free survival and overall survival advantages when treated with the multi-kinase inhibitor cabozantinib. However, since this treatment is costly and is accompanied by significant adverse events in a large proportion of patients, its cost-effectiveness in these patients should be determined. Methods: We developed a Markov model incorporating health outcomes, measured by life-years and quality-adjusted life-years (QALYs) to evaluate the cost-effectiveness of cabozantinib compared with placebo in patients who have failed prior systemic therapy. Results: Treatment with cabozantinib results in a mean gain of 11.6 weeks of life (0.22 life-years) as compared with placebo. When quality of life was incorporated, treatment with cabozantinib produced a gain of 0.16 QALYs. The total mean incremental cost of cabozantinib was US$76,406 per patient. The incremental cost-effectiveness ratio for cabozantinib compared with best supportive care was US$469,374/QALY using the recommended dose of 60 mg cabozantinib daily. Conclusion: Our results suggest that the use of cabozantinib in patients with advanced HCC who have progressed on prior treatment, results in a modest incremental benefit with high incremental costs, suggesting that it is not cost-effective at conventional willingness to pay thresholds.

scholarly journals Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

2021 ◽  
Vol 9 (2) ◽  
pp. e001945 ◽  
Author(s):  
Jeffrey Sum Lung Wong ◽  
Gerry Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Cho Wing Li ◽  
Roland Leung ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Acquired Resistance ◽  
Survival Rates ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Resistance ◽  
Advanced Hcc

BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Effective Treatment Option ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

scholarly journals Mistletoe Extract Viscum Fraxini-2 for Treatment of Advanced Hepatocellular Carcinoma: A Case Series

2021 ◽  
pp. 224-231
Author(s):  
Richard T. Lee ◽  
Peiying Yang ◽  
Asrar Alahmadi ◽  
Jennifer McQuade ◽  
Eric Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Time ◽  
Injection Site Reaction ◽  
Case Series ◽  
Advanced Hepatocellular Carcinoma ◽  
Site Reaction ◽  
Advanced Hcc ◽  
Mistletoe Extract ◽  
Sorafenib Therapy ◽  
Mistletoe Extracts

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of death from cancer worldwide, and for advanced HCC the prognosis is poor. Preliminary studies indicate mistletoe extracts may have anticancer activity for HCC. Methods: A prospective observational case series of advanced HCC patients that chose to take a mistletoe extract called viscum fraxini-2 (VF-2) alone for treatment. Time on treatment, imaging, and laboratory values were collected for descriptive analyses. Results: A total of 12 patients with advanced HCC enrolled onto the protocol, and 10 patients had data available for evaluation. The majority were male (10/12) with a median age of 64 (SD 11). Most patients had received sorafenib therapy (9/12) and had varying Child-Pugh classes (A-4, B-6, C-2). Treatment with VF-2 ranged from 1 to 36 weeks with a mean of 12.3 weeks (SD 12). Six patients received 8 weeks of treatment, and 3 patients received 12 or more weeks of treatment. For patients that received at least 4 weeks of treatment, the average AFP value stabilized during the first 4 weeks of treatment. Two patients experienced an AFP decrease of >30%, approximately 37 and 40% decreases at the nadir. One patient had stable disease of 9 months. Major side effects were fever, fatigue, rash, and local injection site reaction of swelling, redness, and tenderness. Conclusion: This case series of advanced HCC indicates that mistletoe extract VF-2 may have potential biological activity against HCC for selected patients. Research is needed to identify the active compound and predictive markers of response.

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