Health-related quality of life analysis of the LEAP-002 study of lenvatinib plus pembrolizumab versus lenvatinib as first-line treatment for advanced hepatocellular carcinoma

Background: Patients with advanced hepatocellular carcinoma (HCC) have a substantial symptom burden that affects their health-related quality of life (HRQoL). Assessing the impact of first-line regimens on HRQoL is essential to evaluate clinical benefit in addition to efficacy and safety in this setting. Methods: LEAP-002 is a randomized phase III trial of lenvatinib plus pembrolizumab versus lenvatinib plus placebo as first-line treatment for participants with advanced HCC. Patient-reported outcomes (PROs) were prespecified exploratory endpoints assessed in all participants randomly assigned to treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaire (EORTC QLQ-C30), EORTC QLQ Hepatocellular Carcinoma 18-item module (EORTC QLQ-HCC18), and EuroQol 5-dimension, 5-level questionnaire (EQ-5D-5L) at baseline and throughout the trial. Median time to confirmed deterioration (TTD) in PROs was estimated using the Kaplan–Meier method. Least-squares mean change from baseline to week 27 (latest time point when completion and compliance rates were ≥60% and ≥80%, respectively) in PRO scores was assessed using a constrained longitudinal data analysis model. No formal hypotheses were tested. Results: The PRO population comprised 779 participants (lenvatinib plus pembrolizumab, n = 390; lenvatinib plus placebo, n = 389). Completion rates for all PRO assessments were >94% at baseline and >63% at week 27. Median TTD for EORTC QLQ-C30 global health status/quality-of-life score was 11.5 months [95% confidence interval (CI) 5.6 months-not reached] in the lenvatinib plus pembrolizumab group and 4.3 months (95% CI 3.5-5.5 months) in the lenvatinib plus placebo group (hazard ratio 0.80, 95% CI 0.65-0.98). TTD and least-squares mean change from baseline to week 27 were similar between treatment groups for EORTC QLQ-C30 scales, EORTC QLQ-HCC18 scores, and the EQ-5D-5L visual analog scale. Conclusion: Adding pembrolizumab to lenvatinib, which is a current first-line option as a single agent, maintained HRQoL during the first-line treatment of participants with advanced HCC.