Cost effectiveness of regorafenib as second-line therapy for patients with advanced hepatocellular carcinoma : Regorafenib Cost Effectiveness

VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib.

The Panel on Cost-Effectiveness in Health and Medicine has called for an "off-the-shelf" catalogue of nationally representative, community-based preference scores for health states, illnesses, and conditions. A previous review of cost-effectiveness analyses found that 77% did not incorporate community-based preferences, and 33% used arbitrary expert or author judgment. These results highlight the necessity of making a wide array of appropriate, community-based estimates more accessible to cost-effectiveness researchers. To provide nationally representative EQ-5D index scores for chronic ICD-9 codes. The nationally representative Medical Expenditure Panel Survey (MEPS) was pooled (2000-2002) to create a data set of 38,678 adults. Ordinary least squares (OLS), Tobit, and censored least absolute deviations (CLAD) regression methods were used to estimate the marginal disutility of each condition, controlling for age, comorbidity, gender, race, ethnicity, income, and education. Most chronic conditions, age, comorbidity, income, and education were highly statistically significant predictors of EQ-5D index scores. Homoskedasticity and normality assumptions were rejected, suggesting only CLAD estimates are theoretically unbiased. The magnitude and statistical significance of coefficients varied by analytic method. OLS and Tobit coefficients were on average 60% and 143% greater than CLAD, respectively. The marginal disutility of 95 chronic ICD-9 codes as well as unadjusted mean, median, and 25th and 75th percentiles are reported. This research provides nationally representative, community-based EQ-5D index scores associated with a wide variety of chronic ICD-9 codes that can be used to estimate quality-adjusted life-years in cost-effectiveness analyses.

Aside from the multikinase inhibitor sorafenib, there are no effective systemic therapies for the treatment of advanced hepatocellular carcinoma. To assess the efficacy of everolimus in patients with advanced hepatocellular carcinoma for whom sorafenib treatment failed. EVOLVE-1 was a randomized, double-blind, phase 3 study conducted among 546 adults with Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were intolerant of sorafenib. Patients were enrolled from 17 countries between May 2010 and March 2012. Randomization was stratified by region (Asia vs rest of world) and macrovascular invasion (present vs absent). Everolimus, 7.5 mg/d, or matching placebo, both given in combination with best supportive care and continued until disease progression or intolerable toxicity. Per the 2:1 randomization scheme, 362 patients were randomized to the everolimus group and 184 patients to the placebo group. The primary end point was overall survival. Secondary end points included time to progression and the disease control rate (the percentage of patients with a best overall response of complete or partial response or stable disease). No significant difference in overall survival was seen between treatment groups, with 303 deaths (83.7%) in the everolimus group and 151 deaths (82.1%) in the placebo group (hazard ratio [HR], 1.05; 95% CI, 0.86-1.27; P = .68; median overall survival, 7.6 months with everolimus, 7.3 months with placebo). Median time to progression with everolimus and placebo was 3.0 months and 2.6 months, respectively (HR, 0.93; 95% CI, 0.75-1.15), and disease control rate was 56.1% and 45.1%, respectively (P = .01). The most common grade 3/4 adverse events for everolimus vs placebo were anemia (7.8% vs 3.3%, respectively), asthenia (7.8% vs 5.5%, respectively), and decreased appetite (6.1% vs 0.5%, respectively). No patients experienced hepatitis C viral flare. Based on central laboratory results, hepatitis B viral reactivation was experienced by 39 patients (29 everolimus, 10 placebo); all cases were asymptomatic, but 3 everolimus recipients discontinued therapy. Everolimus did not improve overall survival in patients with advanced hepatocellular carcinoma whose disease progressed during or after receiving sorafenib or who were intolerant of sorafenib. clinicaltrials.gov Identifier: NCT01035229.