A 65-year-old man from Bangalore is found to have a 4 cm hepatocellular carcinoma in the setting of cirrhosis (Child-Pugh A). Serum AFP is 8500 ng/mL. He is not a candidate for surgical resection or liver transplantation. What is the drug of choice for first-line systemic therapy?

Explanation

## Hepatocellular Carcinoma Systemic Therapy **Key Point:** Sorafenib is the first-line tyrosine kinase inhibitor (TKI) for advanced HCC, approved by FDA based on the SHARP trial demonstrating survival benefit. ### Why Sorafenib: - Multikinase inhibitor targeting RAF/MEK/ERK and VEGFR/PDGFR pathways - Prolongs median overall survival (10.7 vs. 7.9 months vs. placebo in SHARP) - Improves time to radiological progression - Oral formulation, suitable for outpatient management - Well-tolerated in cirrhotic patients with preserved liver function ### Current HCC Treatment Landscape (2023): | Stage/Setting | First-Line Options | |---------------|-------------------| | Advanced (BCLC C) | Sorafenib, Lenvatinib, Atezolizumab + Bevacizumab | | Intermediate (BCLC B) | TACE, Sorafenib if TACE-refractory | | Early (BCLC A) | Resection, Transplant, Ablation | **Clinical Pearl:** Lenvatinib and atezolizumab + bevacizumab are emerging alternatives with similar or superior efficacy, but sorafenib remains the most widely used and longest-established first-line agent globally.