Cabozantinib in Japanese patients with advanced hepatocellular carcinoma: a phase 2 multicenter study

Masatoshi Kudo,Akiko Kimura,Masafumi Ikeda,Kaoru Tsuchiya,Yoshitaka Inaba,Atsushi Hagihara,Shingo Kuroda,Manabu Morimoto,Junji Furuse,Meguru Achira,Hiroshi Aikata,Naoya Kato,Kazushi Numata,Kenta Motomura,Shunsuke Kondo

doi:10.1007/s00535-020-01753-0

Abstract

BackgroundTo evaluate the efficacy and safety of cabozantinib in Japanese patients with advanced hepatocellular carcinoma (HCC) who had progressed following one or two lines of systemic therapy including sorafenib. An exploratory evaluation in sorafenib-naïve patients was performed.MethodsIn this open-label, single-arm, phase 2 trial, patients received oral cabozantinib 60 mg once daily. The primary endpoint was progression-free survival (PFS) rate at Week 24. Secondary endpoints included PFS, overall survival (OS), objective response rate (ORR, best response of complete/partial response), disease control rate (DCR, objective response or stable disease) and safety.ResultsThirty-four patients received cabozantinib across 17 centers (prior sorafenib cohort, n = 20; sorafenib-naïve cohort, n = 14). PFS rate at 24 weeks was 59.8% [90% confidence interval (CI) 36.1–77.2%] in the prior sorafenib cohort, 16.7% (90% CI 4.0–36.8%) in the sorafenib-naïve cohort and 40.1% (90% CI 24.8–55.0%) overall. Median PFS was 7.4 months for the prior sorafenib cohort, 3.6 months for the sorafenib-naïve cohort, and 5.6 months overall. OS rate at 6 months was 100.0%, 78.6% and 91.1%, respectively; DCR was 85.0%, 64.3% and 76.5%, respectively. The ORR was 0.0% for both cohorts. All patients required dose modifications due to adverse events, the most common of these were palmar–plantar erythrodysesthesia syndrome and diarrhea. Three patients (8.8%) discontinued due to adverse events other than disease progression.ConclusionsCabozantinib 60 mg/day has a favorable benefit/risk profile for Japanese patients with advanced HCC who have previously received one or two lines of systemic anticancer therapy including sorafenib. (Clinical trial registration: NCT03586973)

Highlights

Liver cancer is the fifth-highest cause of cancer-related mortality in Japan, accounting for a total of 40,099 deaths in 2014 [1]
The study was conducted between August 2018 and the data cutoff in July 2019 at 17 Japanese clinical centers
A total of 42 patients with advanced hepatocellular carcinoma (HCC) were assessed for eligibility, of whom eight were excluded during screening (Fig. 1)

Summary

Introduction

Liver cancer is the fifth-highest cause of cancer-related mortality in Japan, accounting for a total of 40,099 deaths in 2014 [1]. Since 2007, standard of care first-line therapy for advanced, unresectable HCC has been systemic treatment with sorafenib monotherapy [4] Both the SHARP and Asia Pacific phase 3 trials showed a significant survival benefit with sorafenib versus placebo in this population, with an approximate 32% reduction in the relative risk of death [5, 6]. The CELESTIAL study population included patients from the Asia–Pacific region, Europe and North America, but did not include patients from Japanese clinical centers [13] The aim of this phase 2 study was to evaluate the efficacy and safety of cabozantinib in Japanese patients with advanced HCC who had received prior sorafenib, including patients who were intolerant to sorafenib. A second cohort of patients was included who had received prior systemic therapy for advanced HCC that did not include sorafenib to be assessed in an exploratory manner

Study design and treatment

Results

Discussion