Cabozantinib for Advanced Hepatocellular Carcinoma in the Latest Real-World Practice: A Multicenter Retrospective Analysis

Abstract

Background Cabozantinib was found to be effective as a second- or third-line treatment after sorafenib in patients with advanced hepatocellular carcinoma (HCC) in the phase 3 CELESTIAL trial. So far, as immunotherapy has substituted molecular target agents as the primary systemic therapy for advanced HCC, cabozantinib is extensively used in the latest real-world clinical practice in a greatly different position than that shown by the CELESTIAL trial. In the current analysis, we examined the safety and effectiveness of cabozantinib administration in real-life settings for patients with advanced HCC. Methods We retrospectively obtained data from patients with advanced HCC who received cabozantinib in three institutions in Japan between 14 September 2018 and 30 November 2021. Results During the study period, 23 patients with advanced HCC received cabozantinib. Our cohort included 21.7% of patients with Child–Pugh class B, and 52.2% of patients in fourth line or later. The median progression-free survival of patients given cabozantinib was 3.7 months. Regarding patients with Child–Pugh class B or administration in fourth line or later, the discontinuation rate due to adverse events in patients who initialized at 40 or 20 mg was lower than those who initialized at 60 mg (42.9% versus 75.0%). Patients who were able to continue treatment with cabozantinib for more than 3 months were more likely to undergo dose reduction than those who did not (85.7% versus 25.0%). Conclusions Cabozantinib has recently been administered to a diverse range of patients, including those who were not enrolled in the CELESTIAL trial. Deliberate dose reduction could potentially offer clinical benefits to patients with impaired liver function. Furthermore, managing adverse events by reducing the dose could play a crucial role in extending the duration of treatment with cabozantinib. The preprint version of this work is available on https://www.researchsquare.com/article/rs-2655181/v1 .

Insights in Molecular Therapies for Hepatocellular Carcinoma

“…This retrospective analysis suggested that dosing lenvatinib based on body weight in patients with advanced HCC successfully upheld efficacy, with similar rates of treatment-emergent adverse events observed in both body weight groups [121]. There are also data for starting therapy with sorafenib and cabozantinib at a reduced dose, which showed a better side effect profile with preserved anti-tumor activity [122][123][124][125][126][127]. Specifically for hand-foot-syndrome, prophylactic application of emollients containing 10% urea, used two to three times daily, has been demonstrated to decrease the occurrence and postpone the onset of hand-foot syndrome in patients undergoing sorafenib treatment [128].…”

Small molecule tyrosine kinase inhibitors approved for systemic therapy of advanced hepatocellular carcinoma: recent advances and future perspectives

“…Second-line cabozantinib had comparable median OS vs. third- or later-line cabozantinib (8.1 vs. 7.0 months; P = 0.88) [ 79 ]. Third- or earlier-line cabozantinib showed similar median OS (3.2 vs. 4.3 months; P = 0.708) but numerically better PFS compared with fourth- or later-line cabozantinib (9.2 vs. 3.7 months; P = 0.148) [ 80 ].…”

“…Third- or earlier-line cabozantinib showed similar median OS (3.2 vs. 4.3 months; P = 0.708) but numerically better PFS compared with fourth- or later-line cabozantinib (9.2 vs. 3.7 months; P = 0.148) [ 80 ].…”

“…Cabozantinib showed a favorible tendency for patients at BCLC stage A or B vs. those at BCLC stage C in terms of median OS (14.1 vs. 6.6 months; P = 0.056) [ 79 ]. Child–Pugh A patients had significantly better median OS (8.5 vs. 3.1 months; P = 0.0053) [ 78 – 80 ], median PFS (4.3–9.2 months vs. 0.5–2.2 months; P ≤ 0.001) [ 78 , 80 ], TTP (2.1 vs. 0.5 months; P < 0.001) [ 80 ], and DCR (71.5% vs. 45.5%; P = 0.021) [ 78 ] compared with Child–Pugh B patients (Table 5 ). Patients with ALBI grade 1 or 2 showed significantly longer OS (13 vs. 5.6 months; P < 0.001) and PFS (6.2 vs. 3.5 months; P = 0.009) than those with ALBI grade 3 [ 78 ].…”