Disparate patterns of disease time burden in patients with HCC on immunotherapy or tyrosine kinase inhibitors

Background & Aims

While cancer survivorship for hepatocellular carcinoma (HCC) has improved, associated disease time burden in patients taking systemic therapies remains poorly understood. In this study, we used days at home (DAH), a patient-centered metric, to compare the disease time burden between patients taking immunotherapies and tyrosine kinase inhibitors (TKIs).

Methods

Patients with HCC receiving systemic therapy from 2008 to 2023 were identified from a population-based cohort. Patients were classified based on the use of immunotherapy (nivolumab, pembrolizumab, atezolizumab, durvalumab, tremelimumab, and ipilimumab; including monotherapies or combinations) or TKIs (lenvatinib, sorafenib, cabozantinib, and regorafenib). The primary outcome was DAH, defined as days alive and not requiring healthcare utilization within the first year of systemic therapy.

Results

This study included 4,677 patients (immunotherapy, 578; TKIs, 3,410; both immunotherapy and TKIs, 689). Compared with TKIs, immunotherapy use was associated with higher 1-year overall survival (58.1% vs. 34.2%, respectively, p <0.001) and higher mean DAH (223.1 vs. 183.3 days, respectively, p <0.001). Immunotherapy was associated with fewer days spent on inpatient stays and emergency department attendance, but more days spent on day procedures and investigations (all p <0.01). Immune-related adverse events (irAEs) occurred in 12.3% of patients taking immunotherapy, and independently predicted lower probability of achieving DAH ≥180 days within the first year of therapy (hazard ratio 0.523, 95% CI 0.290–0.942, p = 0.031). Patients taking immunotherapy with irAEs had comparable DAH to patients taking TKIs (p = 0.469).

Conclusions

Immunotherapy was associated with reduced disease time burden in HCC compared with TKIs. However, this benefit was dampened by the occurrence of irAEs. Our data has quality-of-life implications, and could influence patients’ treatment decisions.

Impact and implications

This study utilized days at home (DAH), a patient-centered metric, to assess the disease time burden in patients with advanced hepatocellular carcinoma taking systemic therapies. We demonstrated that immunotherapy was associated with higher DAH compared with tyrosine kinase inhibitor treatment, although this benefit was dampened by the occurrence of immune-related adverse events. These findings have quality-of-life implications and can be used for patient counselling.