FDA Approves First Biomarker-Driven Drug for HCC

Nick Mulcahy


May 13, 2019

The US Food and Drug Administration (FDA) has approved ramucirumab (Cyramza, Lilly) as monotherapy for the treatment of patients with hepatocellular carcinoma (HCC) who have an alpha-fetoprotein (AFP) level ≥ 400 ng/mL and have been treated with sorafenib.

The approval marks the first time a biomarker-driven therapy has been approved by the FDA for HCC. AFP is a prognostic biomarker assessed using a blood test.

Ramucirumab investigator Andrew X. Zhu, MD, Massachusetts General Hospital Cancer Center, Boston, said that patients with increased AFP concentrations "can have more aggressive disease and a poorer prognosis with increased angiogenesis."

Ramucirumab is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist and has previously been approved for nonsmall cell lung cancer, gastric cancer, and colorectal cancer.

The new approval is based on results from the REACH-2 trial, a randomized, placebo-controlled phase 3 study comparing ramucirumab (n = 197) to placebo (n = 95) in patients with HCC who had been treated with sorafenib and were AFP-high (≥ 400 ng/mL).

Median overall survival, the primary endpoint, in the ramucirumab group was 8.5 months versus 7.3 months for the placebo group (P = .02). Median progression free survival was 2.8 months versus 1.6 months (P < .0001).

The overall response rate was 4.6% among the ramucirumab group and 1.1% in the placebo group. All responses were partial.

Patients received either ramucirumab 8 mg/kg or placebo intravenously every 2 weeks. Patients received a median of six doses of ramucirumab; the median duration of exposure was 12 weeks.

The median age of study participants was 64 years; 80% were men and 50% were Asian. Additionally, 35% had macrovascular invasion; 72% had extrahepatic spread; 17% were sorafenib intolerant; and 64% had prior locoregional therapy.

The most common serious adverse reactions with ramucirumab were ascites (3%) and pneumonia (3%).

Treatment discontinuations because of adverse reactions occurred in 18% of ramucirumab-treated patients, with proteinuria being the most frequent (2%).

The most common adverse reactions reported in 15% or more of patients were fatigue, peripheral edema, hypertension, abdominal pain, decreased appetite, proteinuria, nausea, and ascites. The most common laboratory abnormalities were thrombocytopenia, hypoalbuminemia, and hyponatremia.

The FDA has removed the boxed warning from the ramucirumab label that highlighted warnings pertaining to hemorrhage, gastrointestinal perforation, and impaired wound healing. The updated ramucirumab label continues to provide important information on these specific risks, according to the company.

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