Clinical outcomes and prognostic factors of patients with advanced hepatocellular carcinoma treated with sorafenib as first-line therapy : A Korean multicenter study Journal of Gastroenterology and Hepatology R3. 최하나 /Pf. 심재준

Introduction Hepatocellular carcinoma –the 5 th most common cancer –3 rd leading cause of cancer death worldwide Sorafenib (Nexavar,Germany) –An oral multikinase inhibitor –Suppress tumor growth and angiogenesis Raf/mitogen-activated protein kinase Extracellular signal-regulated kinases signaling pathway Receptor tyrosine kinases : vascular endothelial growth factor receptor platelet-derived growth factor receptor-β

6.5 vs 4.2months2.8 vs 1.4months

Limitation of sorafenib 1.Overall survival 2.Adverse 3.high cost 4.policies

Methods Patient eligibility 2007 ~2012 Total 118 → 86 patients were included Inclusion criteria Age : 20 ~ 75 years old Barcelona Clinic Liver Cancer (BCLC) C stage Child–Pugh class A and B Eastern Cooperative Oncology Group performance status 0 ∼ 2 The duration of sorafenib administration (≥ 2weeks) Lab findings adequate for systemic chemotherapy : WBC ≥ 2000/mm3, PLT count ≥ 50 × 10 9 /L, Hb level ≥ 8.5 g/dL, and Cr < 1.5 mg/dL

Diagnosis of HCC the Korea Liver Cancer Study Group A one or more risk factors (HBV,HCV, cirrhosis) and one of the following: (i) AFP > 400 ng/mL and a positive finding on at least one of three typical imaging studies(CT, MRI, angiography) (ii) AFP< 400 ng/mL and positive findings on at least two of the three imaging studies.

Treatment and assessment of therapeutic responses 400 mg oral sorafenib twice daily significant radiological or clinical progression or intolerable toxicity Dose reduction of sorafenib (i.e. 400 mg once daily, 400 mg every other day) : drug-related grade 3/4 toxicities the National Cancer Institute Common Toxicity Criteria version 3.0.

Statistical analysis Primary end-point : OS Secondary end-points : PFS and treatment-related toxicity SAS software (ver )

Results Patients’ characteristics

Safety The median duration of sorafenib : 2.4 (range 0.5–36.1) months the median cumulative dosage : 26,500 (range 10,560–268,200) mg

Factors associated with OS

Factors associated with PFS

Treatment after cessation of sorafenib After the cessation of sorafenib due to disease progression or toxicity, only two patients underwent systemic chemotherapy for clinical studies, whereas the remaining subjects received best supportive care. The duration from systemic chemotherapy to death was 23 and 8 months, respectively.

Conclusions Because the efficacy of sorafenib seems marginal in Korean patients with treatment-naïve HCC, how to select candidates with favorable outcomes should be further investigated.