A retrospective single centre study exploring the efficacy of sequential tyrosine-kinase inhibitors (TKI) for patients with hepatocellular carcinoma. Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. In the UK patients with advanced or intermediate disease despite locoregional treatments are offered a tyrosine-kinase inhibitor (TKI). Sorafenib (SOR) remains the approved first-line choice, with lenvatinib (LEN) and regorafenib (REG) used as either alternative first line or second line therapies, respectively. Previous studies have shown increased overall survival when comparing a single drug to placebo; however few have studied outcomes for patients treated with one or more TKIs. Methods: Data was collected from patients who received TKI therapy for HCC between January, 2016 and September, 2020, within the Barts Health NHS Trust, London. The Electronic Medical Record system was used to gather information pertaining to treatment. The non-parametric Pearson correlation coefficient was calculated using IBM SPSS software to explore the duration of TKI therapy and overall survival. Results: 64 patients were included in the cohort, 17% (n=11) female, 83% (n=53) were male. Median age was 68 years (range 38 - 92 years) and median survival from diagnosis was 18 months (range 4 - 106 months). 51 patients received one TKI, 12 patients received two and 1 patient received three sequential TKIs There was no significant correlation between the number of cycles of SOR or LEN received and overall survival (p = 0.387), but there was a statistically significant correlation in the group of patients who received SOR and then REG (r_s = 0.973, p = 0.000). There was also a statistically significant correlation (r_s = 0.360, p = 0.004) between the cumulative number of cycles of TKI treatment and overall survival for all patients (i.e. SOR only, LEN only and those who received more than one TKI). Conclusions: Our analysis suggests that across the cohort, a longer duration of TKI treatment (measured in cycles) may be associated with increased overall survival for patients with advanced HCC. Further data is required to explore the impact on quality of life during therapy.

Key: SOR = Sorafenib, LEN = Lenvatinib, REG = Regorafenib. Treatment duration measured to the nearest 0.5 cycles.