Time-toxicity of first-line systemic therapy for hepatocellular carcinoma in clinical practice.

4145 Background: Combination immunotherapy has become a standard first-line systemic treatment for hepatocellular carcinoma (HCC). While efficacy outcomes have been well described, the treatment-related time burden experienced by patients, including frequent hospital visits and admissions, has not been sufficiently evaluated in real-world clinical practice. Aims: To evaluate time toxicity as a patient-centered measure of treatment burden and to identify baseline factors associated with high time toxicity in patients receiving first-line combination immunotherapy for HCC. Methods: This retrospective observational study included patients with HCC who received first-line combination immunotherapy (atezolizumab + bevacizumab or durvalumab + tremelimumab) at our institution by April 2025. The observational period was defined as the treatment duration plus 28 days. Time toxicity (TT) was calculated as the proportion of days requiring hospital contacts, including scheduled visits, management of adverse events, and hospital admissions. High time toxicity (hTT) was defined as TT ≥20%, representing a clinically meaningful high treatment burden. Factors associated with hTT were examined using multivariate logistic regression analysis. Results: A total of 126 patients were included, with a median age of 74 years (IQR 67–81). The median observational period was 178 days (IQR 75-287), the median total hospital contacts was 20 days (IQR 13-30) and the median inpatient days was 7 days (IQR 4-14). Moreover, the median TT was 11.8% (IQR 9.1–17.9) and 23.0% of all patients experienced hTT. In multivariate analysis, impaired liver function (mALBI grade 2b–3; OR 7.17, 95% CI 2.60–19.80) and AFP ≥100 ng/mL (OR 3.03, 95% CI 1.20–7.67) were independently associated with hTT. Conclusions: Patients with impaired liver function and elevated AFP levels experienced a significantly higher treatment-related time burden during first-line combination immunotherapy for HCC. Assessment of time toxicity may provide clinically meaningful information to support shared decision-making, particularly in elderly or vulnerable patient populations.