Currently Viewing:
Evidence-Based Oncology February 2019
Rutgers' Janice Mehnert, MD, on Biomarkers, Being Inclusive in Clinical Trials, and Taking Time to Weigh the Options
Mary Caffrey
Is Immunotherapy the Future of Glioblastoma Treatment?
Samantha DiGrande
Finding the Right Combination for Neoadjuvant Therapy in High-Risk, Stage III Melanoma
Mary Caffrey
Moving Toward the "Tipping Point" for Transformation in Cancer Care
Mary Caffrey
Medical World News: Clinical Updates
Coverage by Jaime Rosenberg, Laura Joszt, Samantha DiGrande, and Kelly Davio
Medical World News: Regulatory Updates
Coverage by Jaime Rosenberg, Laura Joszt, Samantha DiGrande, and Kelly Davio
AJMCtv® Interviews, February 2019
Currently Reading
Humanistic and Economic Burden of Hepatocellular Carcinoma: Systematic Literature Review
Christine G. Kohn, PharmD; Prianka Singh, PharmD, MPH; Beata Korytowsky, MA; Jonathan T. Caranfa, PharmD; Jeffrey D. Miller, MS; Bruce E. Sill, PharmD, MS; Alexander C. Marshall, PharmD, MPH; Neehar D. Parikh, MD, MS

Humanistic and Economic Burden of Hepatocellular Carcinoma: Systematic Literature Review

Christine G. Kohn, PharmD; Prianka Singh, PharmD, MPH; Beata Korytowsky, MA; Jonathan T. Caranfa, PharmD; Jeffrey D. Miller, MS; Bruce E. Sill, PharmD, MS; Alexander C. Marshall, PharmD, MPH; Neehar D. Parikh, MD, MS
Worldwide, more than half a million new cases of hepatocellular carcinoma (HCC) are diagnosed annually. The incidence of HCC in the United States is rising with an estimated 31,000 new cases in 2018. Disease prognosis remains poor, with a 5-year survival rate across all disease stages estimated between 10%-20%, and 3% for those diagnosed with distant disease. Although morbidity is significant, especially among patients with advanced-stage disease, limited information exists on the humanistic and economic burden of HCC.
OBJECTIVE: Worldwide, more than half a million new cases of hepatocellular carcinoma (HCC) are diagnosed annually. The incidence of HCC in the United States is rising with an estimated 31,000 new cases in 2018. Disease prognosis remains poor, with a 5-year survival rate across all disease stages estimated between 10%-20%, and 3% for those diagnosed with distant disease. Although morbidity is significant, especially among patients with advanced-stage disease, limited information exists on the humanistic and economic burden of HCC.
STUDY DESIGN: Systematic literature review.
METHODS: A systematic literature search was conducted using MEDLINE and Embase computerized databases January 1, 2007, to November 1, 2017) to identify studies that evaluated adult HCC populations and quantified humanistic (utility or patient-reported) or economic (costs or resource-utilization) outcomes.
RESULTS: Fifty-seven studies met the inclusion criteria. Overall quality of life (QOL) reported by patients with HCC is poor; those with advanced disease have lower health status/QOL scores compared with those diagnosed at earlier stages of disease. HCC imposes a substantial healthcare resource utilization and cost impact on both patients and payers in the United States. Direct costs of HCC reported in the reviewed literature varied considerably.
CONCLUSIONS: The economic and humanistic burden of HCC in the United States is substantial. Patients need effective new therapies that prolong survival and positively affect QOL. Healthcare payers need to consider clinical outcomes while balancing economic and QOL implications. With the advent of new therapies, particularly immuno-oncology (I-O) therapies, additional research is needed to gain understanding of the economic and humanistic aspects of HCC and its treatment.


 
METHODS:

A systematic literature search was conducted using the MEDLINE and Embase computerized databases from January 1, 2007, to November 1, 2017. This time frame allowed identification of studies performed in the past decade, while excluding older studies using outdated or nonguideline recommended treatments. The search strategy is available in eAppendix 1.

Two investigators independently reviewed all citations and screened all potentially relevant, full-text articles for inclusion using a priori defined criteria, with disagreement resolved through discussion. To be eligible for inclusion, studies had to: employ an observational or experimental study design; evaluate a treated adult HCC population; provide data quantifying economic (costs or resource utilization) or QOL outcome data; and be an English-language, full-text publication. Studies investigating treatments for HCC were required to use an evidence-based or standard-of-care approach. Additional inclusion/exclusion criteria are available in eAppendix 2. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram is depicted in eAppendix 3.6

RESULTS:

The initial search yielded 2147 nonduplicate citations (eAppendix 3), of which 57 studies representing 59 analyses met the inclusion criteria. Of these, 5 were included in health utility analyses (Table 17-11), 24 in patient- reported outcome (PRO) and QOL analyses (Tables 2 [part A and part B]7,9,12-33 and 3 [part A, part Bpart C, and part D]7,9,12-33), 14 in costs and resource utilization analyses (Tables 4 [part A and part B]34-47 and 5 [part A and part B]34-47), and 16 in cost-effectiveness analyses (eAppendices 4-848-53).

Humanistic Burden

Health Utility Analyses/Measures. 
Utility measures are expressed as a numeric value from 0 to 1, with 0 representing death and 1 representing perfect health.54 Five studies reported health utility values among patients with HCC, with lower scores among patients with advanced HCC (aHCC), even while on systemic treatment.7-11 Although clinical trial data evaluating utilities in HCC exist,7-9 there is a lack of comparable real-world utility data for these patients (Table 1).

Levy et al interviewed patients with hepatitis B virus (HBV) infection and uninfected respondents using health-state descriptions related to HBV infection (HBV combined with compensated and decompensated cirrhosis, HCC, and liver trans- plantation) to elicit health utility scores.11 HCC was among the health states with the lowest mean health utility score in these patients.11 Similarly, a study in Canadian patients with HCC and HBV found that lower QOL scores in this population were associated with cirrhosis and HCC, rather than with the infection itself.10 This study reported values of 0.77 to 0.85 for patients with HCC and HBV, depending on the utility assessment instrument used.10

Three multicenter, randomized controlled trials (RCTs) reported utility values in patients with aHCC categorized as Child-Pugh class A with Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.7-9 Although no statistical analysis was provided, utility values declined as treatment continued.

QOL. Twenty-four studies reported results related to PRO measures evaluating QoL and symptoms in patients with HCC7,9,12-33; US-only populations were included in 10 studies (Tables 2 and 3). A detailed summary of the data can be found in eAppendix 9.

QOL in aHCC Populations. Patients with aHCC have lower global health scores compared with patients who are diagnosed at earlier stages of disease; the median European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) score in Barcelona Clinic Liver Cancer (BCLC) stage A disease is 54, declining to 47 and 39 for stages B/C and D, respectively.23 Kaiser et al reported that 90% of patients with aHCC identified pain as an important concern, which often caused significant functional limitations. In most cases, pain was ongoing and began within 6 months of diagnosis. Other concerns included common symptoms of HCC: diarrhea, fatigue, and loss of appetite; skin toxicity also appeared to be a key issue. It is important to note that most patients in this study received treatment with sorafenib.22 A small study (n = 18) found that outpatients with aHCC nearing end-of-life reported pain and lack of energy as their most frequent and distressing symptoms; other symptoms included drowsiness and problems with sexual interest or activity.12

QOL in HCC Therapies. QOL can reflect benefits or harms associated with therapeutic interventions from a patient perspective. Using the Medical Outcomes Study Short Form 36 (SF-36), previously untreated patients with HCC reported improved mental health during the first 4 months of treatment with transarterial chemoembolization (TACE) and showed improvement in bodily pain, but worsening vitality scores, after the first TACE procedure.31 Hinrichs et al prospectively evaluated QOL in 79 patients before and 2 weeks after TACE. Patients reported a 12.1% decrease in global health, as well as major decreases in role, physical, and social functioning; life-impairing symptoms including pain, loss of appetite, and fatigue increased, compared with baseline.13 Doxorubicin drug-eluting bead TACE (DEB-TACE) demonstrated long-term preservation of QOL among previously untreated patients with HCC with no significant change in any SF-36 domain at 3, 6, and 12 months post–DEB-TACE compared with baseline.17 A prospective observational study suggested that, despite having more advanced disease (higher tumor burden and BCLC stage), patients with HCC who received yttrium-90 (Y90) radioembolization showed significant increases in several QOL domains, driven in part by social and functional well-being, compared with TACE-treated patients.28 Chie et al reported that QOL outcomes were similar in HCC patients receiving surgery or embolization, while ablation was less effective at maintaining QOL.17

In an RCT comparing sorafenib to selective internal radiotherapy (SIRT) with Y90 in patients with locally advanced or intermediate-stage HCC previously treated with TACE, the global health status subscore was significantly better in the SIRT group versus the sorafenib group.15 In a multicenter, multinational phase 2 trial, HCC patients receiving combination therapy with sorafenib and everolimus reported a greater decrease in physical well-being and mood, compared with those receiving sorafenib alone, despite worse baseline mood scores in the latter group.16 Finally, a small, real-world study of sorafenib in patients with aHCC reported significantly decreased overall and domain QOL scores and severe drug-related adverse events (eg, fatigue, hand-foot-skin reaction, throm- bocytopenia), leading to a cumulative therapy discontinuation rate of 33%.25

Economic Burden

Costs and Healthcare Resource Utilization.
 
Fourteen studies reported results related to costs or resource utilization associated with HCC in the United States (Table 4, eAppendix 10).34-47

Direct Costs. Direct cost outcomes varied markedly across the studies (Table 5). For studies reporting overall direct costs for patients with HCC regardless of stage or treatment, per patient per year (PPPY) costs ranged from $29,35447 to $58,529,45 with median overall costs of up to $176,456 per patient.39

Reported costs varied by stage of disease at diagnosis and by age. In the Surveillance, Epidemiology, and End Results (SEER) registries and linked Medicare (SEER-Medicare) database, 15-year direct costs for HCC were estimated at $54,829, with the highest costs incurred by those with localized disease ($78,553), followed by regional ($49,492) and distant disease ($34,352).44 In contrast, patients with distant HCC had the highest mean total per patient per month (PPPM) costs ($9585) followed by regional ($8072) and localized disease ($7265); inpatient stays and physician visits were the primary cost drivers.44 Another SEER-Medicare study found that localized disease accounted for the highest proportion (44.5%) of the total cost of illness, followed by regional (31%) and distant disease (14%).47 The authors reported that, across age strata, younger patients generally incur higher healthcare costs than older patients.47 

 
Copyright AJMC 2006-2019 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up