The U.S. Food and Drug Administration ( FDA ) has approved Cyramza ( Ramucirumab injection, 10 mg/mL solution ), as a single agent, for the treatment of patients with hepatocellular carcinoma ( HCC ) who have an alpha-fetoprotein ( AFP ) of greater thanor equal to 400 ng/mL and have been treated with Sorafenib ( Nexavar ).
Concurrent with this approval, the FDA has also removed the boxed warning from the Cyramza labeling.
Hepatocellular carcinoma is the most common form of liver cancer, which is the fourth-leading cause of cancer-related death worldwide.
In the U.S., liver cancer is one of the few major cancers with incidence rates that continue to rise every year and is the fastest rising cause of cancer death.
AFP is a prognostic biomarker that can be assessed through a simple blood test, now allowing physicians to select patients who may benefit from treatment and to monitor disease progression in advanced hepatocellular carcinoma.
This approval is based on the results from the REACH-2 study, the first positive phase 3 hepatocellular carcinoma trial in a biomarker-selected patient population.
REACH-2 is a global, randomized, double-blind, placebo-controlled phase 3 study of Cyramza compared to placebo in patients with hepatocellular carcinoma who have been treated with Sorafenib and are AFP-High ( AFP greater than or equal to 400 ng/mL ).
The FDA has removed the boxed warning from the Cyramza labeling which highlighted warnings pertaining to hemorrhage, gastrointestinal perforation and impaired wound healing.
The updated Cyramza labeling continues to provide important information on these specific risks, as well as other adverse events.
The labeling for Cyramza contains warnings and precautions for hemorrhage and gastrointestinal hemorrhage, including severe and sometimes fatal events; gastrointestinal perforations, a potentially fatal event; impaired wound healing; arterial thromboembolic events, including serious and sometimes fatal events; hypertension; infusion-related reactions; worsening of pre-existing hepatic impairment, reversible posterior leukoencephalopathy syndrome ( RPLS ); proteinuria including nephrotic syndrome; thyroid dysfunction; and embryo-fetal toxicity.
Cyramza should be permanently discontinued in patients who experience severe bleeding, a gastrointestinal perforation, an arterial thromboembolic event, uncontrolled hypertension, RPLS, or nephrotic syndrome.
Cyramza should be withheld prior to surgery and discontinued if a patient develops wound healing complications.
The most common adverse reactions ( all grades ) observed in single agent Cyramza-treated HCC patients at a rate of greater than or equal to 15% and greater than or equal to 2% higher than placebo were fatigue ( 36% vs 20% ), peripheral edema ( 25% vs 14% ), hypertension ( 25% vs 13% ), abdominal pain ( 25% vs 16% ), decreased appetite ( 23% vs 20% ), proteinuria ( 20% vs 4% ), nausea ( 19% vs 12% ), ascites ( 18% vs 7% ). ( Xagena )
Source: Lilly, 2019