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Patient preferences for unresectable hepatocellular carcinoma (HCC) treatments: Balancing overall survival and quality of life
Background
Atezolizumab plus bevacizumab has become the new standard-of-care treatment option for unresectable HCC, replacing oral tyrosine kinase inhibitors (e.g., sorafenib, lenvatinib). As these treatments have varying benefit-risk profiles and routes of administration, we aimed to quantify patients’ benefit-risk preferences for attributes associated with various first-line systemic treatments for unresectable HCC and estimate the minimum acceptable additional months of overall survival (OS) patients would require in exchange for specific treatment-related adverse events.
Methods
A cross-sectional, web-based discrete-choice experiment (DCE) survey was developed. The survey development was informed by qualitative interviews with patients, published literature and treatment guidelines, expert clinical opinion, and cognitive debriefing interviews. Respondents answered nine DCE questions. Each question offered a choice between two hypothetical treatment profiles created by an experimental design and defined by six attributes with varying levels: OS, number of months to maintain daily function, severity of palmar-plantar syndrome, severity of hypertension, risk of bleeding in the digestive tract, and mode and frequency of administration. Data were analyzed using a random-parameters logit model, and results were used to calculate the minimum number of additional months of OS required to offset worse levels of adverse events.
Results
Between August 30, 2021, and October 14, 2021, patients with self-reported unresectable HCC in the United States (N = 200) completed the survey. Mean age was 59 years, 25.0% were White, 41.5% had at least a 4-year college degree, 33.5% reported less than $50,000 annual income, 93.0% were diagnosed less than 5 years ago, 23.0% reported needing help taking care of themselves, 85.5% were currently receiving treatment for their HCC, 51.5% of those currently receiving medicines by intravenous infusion, and 71.3% by oral pills. On average, patients regarded an additional 10 months of maintaining daily function without decline to be as important or more important than an additional 10 months of OS, indicating a willingness to trade off months of maintaining daily function for months of OS. Among the adverse events, respondents placed the most importance on avoiding moderate-to-severe palmar-plantar syndrome and hypertension, requiring an average of more than 10 additional months of OS to offset the increased burden of these two adverse events. Respondents placed the least importance on a 5-percentage-point reduction in the risk of bleeding in the digestive tract (from 2% to 7%), requiring only 1.6 (confidence interval, 0.04-3.17) additional months of OS to offset this change. Additionally, more convenient dosing (e.g., daily oral pill vs. IV infusion every 3 weeks) was less important to respondents than OS, maintenance of daily function, and avoiding severe instances of palmar-plantar syndrome or hypertension.
Conclusions
Patients with unresectable HCC prioritized avoiding side effects that would severely impact their quality of life during treatment much more compared with mode and frequency of treatment administration and digestive tract bleeding risk. For patients with unresectable HCC, the ability to maintain quality of life and conduct daily activities is as important or more important than a treatment’s survival benefit.
Legal entity responsible for the study
The authors.
Funding
This study was funded by Genentech Inc.
Disclosures
D. Li: Advisory / Consultancy: Merck, Genentech, Exelixis; Speaker Bureau / Expert testimony: Eisai, Exelixis, Ipsen; Research grant / Funding (institution): AstraZeneca, Brooklyn Immunotherapeutics. A. Tan: Shareholder / Stockholder / Stock options: Genentech; Full / Part-time employment: Genentech. S. Hernandez: Full / Part-time employment: Genentech. N. Reilly: Full / Part-time employment: Genentech. All other authors have declared no conflicts of interest.
