Second-line treatment of advanced hepatocellular carcinoma: Time for more individualized treatment options?

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease. It is an aggressive disease that often progresses rapidly when it fails to respond to treatment. As such, patients have limited opportunities to try different subsequent-line treatment regimens. In the last 5 years, the number of agents and/or regimens available for the treatment of advanced HCC has significantly increased, which has made treatment choices for this patient population increasingly complex. In the second-line setting, several phase III trials of regorafenib (RESORCE), ramucirumab (REACH/REACH-2), and cabozantinib (CELESTIAL) have demonstrated clinically meaningful survival benefits in patients with the disease. However, the median overall survival of patients with advanced HCC remains unchanged at approximately 12 mo from the start of systemic second-line therapy, with a limited duration of response. Evidence from the REACH/REACH-2 trials demonstrated for the first time that baseline alpha-fetoprotein (AFP) levels can be used as an identification factor to select those who are likely to benefit the most from ramucirumab treatment. Ramucirumab is both well tolerated and efficacious and has a clinically acceptable safety profile. Therefore, it should be considered an option for patients with AFP levels ≥ 400 ng/mL.