On 10 May 2019, the FDA approved single agent ramucirumab (Cyramza®, Eli Lilly) for the treatment of hepatocellular carcinoma (HCC) patients previously treated with sorafenib and who have an alpha-fetoproteintein (AFP) of ≥400 ng/mL.

REACH-2

The FDA approval was based on data of the multinational, double-blind, placebo-controlled, multicentre REACH‑2 (NCT02435433) study that randomised 292 advanced HCC patients with AFP ≥400 ng/mL and disease progression on or after prior sorafenib or intolerant to sorafenib. Participants were randomised (2:1) to receive either ramucirumab plus best supportive care (BSC) or placebo plus BSC until disease progression or the occurrence of unacceptable toxicity. The primary efficacy endpoint was the overall survival (OS).

The REACH-2 trial showed a significant improvement in the estimated median OS, measuring 8.5 months (range: 7.0-10.6) for patients receiving ramucirumab plus BSC vs 7.3 months (range: 5.4-9.1)  for patients receiving placebo plus BSC (HR=0.71; 95% CI, 0.53-0.95; P=0.020).

Safety

Common adverse reactions in ≥15% of HCC patients receiving single-agent ramucirumab, and with a ≥2% higher incidence when compared to placebo, included fatigue, peripheral oedema, hypertension, abdominal pain, decreased appetite, proteinuria, nausea, and ascites. Common laboratory abnormalities occurring in ≥30% of patients, and with a ≥ 2% higher incidence when compared to placebo) were hypoalbuminemia, hyponatremia, and thrombocytopenia.

Full prescribing information Cyramza®.