Sorafenib Monotherapy vs. TACE-sorafenib Sequential Therapy for HCC With Metastasis

Comparison of Efficacy Between Sorafenib Monotherapy vs. Transarterial Chemoembolization -Sorafenib Sequential Therapy in Hepatocellular Carcinoma Patients With Extrahepatic Metastasis

Sorafenib is the standard therapy for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, addition of transarterial chemoembolization (TACE) may be beneficial for controlling intrahepatic tumour. The investigators aimed to compare the efficacy between the sorafenib monotherapy and TACE-sorafenib sequential therapy in HCC patients with EHM.

Sorafenib is the standard therapy for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, transarterial chemoembolization (TACE) which is a standard therapy for intermediate stage may be beneficial for controlling intrahepatic tumour, thereby providing chance of improving survival in HCC patients with EHM. The investigators aimed to compare the efficacy between the sorafenib monotherapy and TACE-sorafenib sequential therapy in HCC patients with EHM. This study is a prospective randomized controlled study being conducted at 6 tertiary hospitals in South Korea. HCC patients with EHM are being enrolled and randomized into sorafenib monotherapy or TACE-sorafenib sequential therapy group. Patients with main portal vein invasion, Child-Pugh class B or C, and history of TACE or previous systemic therapy are being excluded. The sorafenib monotherapy group receives sorafenib immediately after randomization while the TACE-sorafenib group receives 2~4 times of TACE before starting sorafenib. Response evaluation are performed every 2 months, and time to progression (TTP), progression free survival (PFS), median survival time (MST), and overall survival (OS) which is the primary outcome measure will be compared.

TACE(transarterial chemoembolization )-sorafenib group receives 2~4 times of TACE before starting sorafenib.

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years)

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years)

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years)

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to Feb 28, 2020 (maxium duration: up to 8 years)

Inclusion Criteria: Patients with hepatocellular carcinoma by the European Association for the Study of the Liver (EASL) criteria or pathology One or more extrahepatic metastatic lesion by proven radiologically or histologically No serious coagulation abnormalities Performance status 0 or 1 by Eastern Cooperative Oncology Group(ECOG) criteria Child-Pugh score 5 or 6 Serum creatinine <1.5mg/dL Age between 18 ~ 75 years old No other life-threatening medical illness Exclusion Criteria: Patients with main portal vein invasion Child-Pugh class B or C History of TACE or previous systemic chemotherapy including sorafenib Age >75 years old Cardiovascular diseases History of gastrointestinal bleeding within 2 weeks

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