Eli Lilly has announced that the FDA ( Food and Drug Administration ) has approved Cyramza ( Ramucirumab ) as a single-agent treatment for patients with advanced or metastatic gastric cancer or gastroesophageal junction ( GEJ ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or Platinum-containing chemotherapy.
With this approval, Cyramza becomes the first FDA-approved treatment for patients in this setting.
The Cyramza ( Ramucirumab injection 10 mg/mL solution ) approval is based on results of REGARD, a multicenter, randomized, placebo-controlled, double-blind trial of patients with locally advanced or metastatic gastric cancer including GEJ adenocarcinoma previously treated with fluoropyrimidine- or Platinum-containing chemotherapy.
It is the first Phase III trial to show improved overall survival and progression-free survival with a biologic agent in advanced gastric cancer after prior chemotherapy.
Results have demonstrated that Cyramza ( 8 mg/kg by infusion every two weeks ) plus best supportive care ( BSC ), as compared to placebo plus BSC, increased the median overall survival of patients with advanced gastric cancer by 37% ( median overall survival of 5.2 months [ 95% confidence interval (CI) 4.4, 5.7 ] vs. 3.8 months [ 95% CI 2.8, 4.7 ] for placebo, P=0.047, hazard ratio 0.78 [ 95% CI 0.60, 0.998 ] ).
Additionally, Cyramza has significantly improved progression-free survival, demonstrating a 62% increase in median progression-free survival ( 2.1 months [ 95% CI 1.5, 2.7 ] vs. 1.3 months [ 95% CI 1.3, 1.4 ] for placebo, P less than 0.001, hazard ratio 0.48 [ 95% CI 0.38, 0.62 ] ).
The labeling for Cyramza contains a Boxed Warning regarding increased risk of hemorrhage, including severe and sometimes fatal events. Cyramza should be discontinued in patients who experience severe bleeding.
The most commonly reported adverse reactions ( all grades ) in REGARD, occurring in at least 5% of patients receiving Ramucirumab and at a rate at least 2% higher than those receiving placebo, were hypertension ( 16% vs 8% ), diarrhea ( 14% vs 9% ), headache ( 9% vs 3% ), and hyponatremia ( 6% vs 2% ).
The most common serious adverse events with Ramucirumab were anemia ( 3.8% ) and intestinal obstruction ( 2.1% ). Red blood cell transfusions were given to 11% of Ramucirumab-treated patients vs 8.7% of patients who received placebo.
Across clinical trials of Ramucirumab administered as a single agent, clinically relevant adverse reactions ( including Grade greater than or equal to 3 ) reported in Ramucirumab-treated patients included proteinuria, gastrointestinal perforation, and infusion-related reactions.
In REGARD, according to laboratory assessment, 8% of Ramucirumab-treated patients developed proteinuria versus 3% of placebo-treated patients. Two patients discontinued Ramucirumab due to proteinuria.
The rate of gastrointestinal perforation in the REGARD trial was 0.8% and the rate of infusion-related reactions was 0.4%.
Ramucirumab is a vascular endothelial growth factor ( VEGF ) Receptor 2 antagonist that specifically binds VEGF Receptor 2 and blocks binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. VEGF Receptor 2 is an important mediator in the VEGF pathway.
In an in vivo animal model, Ramucirumab inhibited angiogenesis. Angiogenesis is a process by which new blood vessels form to supply blood to normal healthy tissues as well as tumors, enabling the cancer to grow.
Gastric cancer is a major health problem. It is the fifth most common cancer in the world and is the third-leading cause of cancer death. There were nearly one million new cases worldwide in 2012 ( 631,000 men, 320,000 women ) with approximately 723,000 deaths ( 469,000 men, 254,000 women ).
In the U.S., it is estimated that approximately 22,000 people will be diagnosed with gastric cancer in 2014.
Gastric cancer develops slowly, usually over many years, and often goes undetected. As stomach cancer advances, it can travel through the bloodstream and spread to organs such as the liver, lungs, and bones.
The most common type of stomach cancer is called adenocarcinoma, which starts from one of the common cell types found in the lining of the stomach. ( Xagena )
Source: Lilly, 2014