Masatoshi Kudo1, Kaoru Tsuchiya2, Naoya Kato3, Atsushi Hagihara4, Kazushi Numata5, Hiroshi Aikata6, Yoshitaka Inaba7, Shunsuke Kondo8, Kenta Motomura9, Junji Furuse10, Masafumi Ikeda11, Manabu Morimoto12, Meguru Achira13, Shingo Kuroda14, Akiko Kimura15. 1. Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan. m-kudo@med.kindai.ac.jp. 2. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan. 3. Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan. 4. Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan. 5. Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan. 6. Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 7. Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan. 8. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. 9. Department of Hepatology, IIZUKA HOSPITAL, Iizuka, Japan. 10. Department of Medical Oncology, Faculty of Medicine, Kyorin University, Tokyo, Japan. 11. Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 12. Department of Hepatobiliary Pancreatic Oncology, Kanagawa Cancer Center, Kanagawa, Japan. 13. Clinical Pharmacology, PRA Development Center KK, Osaka, Japan. 14. Biostatistics, Takeda Pharmaceutical Company Limited, Osaka, Japan. 15. Oncology Clinical Research Department, Oncology Therapeutic Area Unit for Japan and Asia, Takeda Pharmaceutical Company Limited, Osaka, Japan.
Abstract
BACKGROUND: To 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. METHODS: In 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. RESULTS: Thirty-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. CONCLUSIONS: Cabozantinib 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).
BACKGROUND: To 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. METHODS: In 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. RESULTS: Thirty-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. CONCLUSIONS: Cabozantinib 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).