OBJECTIVES: To determine whether individual items on the EORTC-QLQ-C30 and hepatocellular carcinoma subscale are associated with statistically significant differences over the course of treatment for patients with unresectable hepatocellular carcinoma (uHCC).

METHODS: This was a multicenter, randomized, open-label, non-inferiority Phase 3 study comparing lenvatinib (LEN) to sorafenib (SOR) as first-line uHCC systemic treatments. 954 patients were randomized to LEN (N=478) or SOR (N=476). Analyses on the individual items of the EORTC QLQ-C30 and HCC18, were conducted using longitudinal generalized estimation equations (GEE) of the post-baseline, treated period assessments for these items. Forest plots of the odds ratios (OR) and associated confidence intervals (CI) from the GEE analyses were generated to characterize the likelihood of a 2-grade categorical deterioration (eg, deteriorate by 2 categories on the verbal response scale) on individual items for patients treated with LEN compared to SOR during the treatment period.

RESULTS: The likelihood of patients experiencing a 2-grade deterioration over the course of the post-baseline treatment period was statistically equivalent for most EORTC-QLQ-C30 and HCC18 items (OR ~ 1.0) with the exception of pain in the shoulder, weight being too low, and reduced activity. Patients treated with SOR were 38% less likely to observe a 2-grade deterioration in shoulder pain (OR=0.7107, CI=0.5611-0.9003, p-value=0.0046). Patients treatment with LEN were 25% less likely to observe a 2-grade deterioration in weight being too low (OR=1.2502, CI=1.0014-1.5609, p-value=0.0485) and 27% less likely to observe a 2-grade deterioration in activity reduction (OR=1.2658, CI=1.0158-1.5774, p-value=0.0358).

CONCLUSIONS: These data provide detailed information on the cumulative probability of categorical deterioration of individual items on the EORTC-QLQ-C30 and HCC18. These results show a similar trend with additional benefit of LEN in terms of anorexia or activity over the course of treatment, which are two key areas for patients especially the ability to perform activities.