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FDA OKs Stomach Cancer Drug Cyramza (Ramucirumab)
The FDA has approved Cyramza (ramucirumab injection, Eli Lilly) 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. Cyramza is the first FDA-approved treatment for patients in this setting.
The agency’s approval was based on results from the phase III REGARD trial, a multicenter, randomized, placebo-controlled, double-blind study of 355 patients with locally advanced or metastatic gastric cancer, including GEJ adenocarcinoma, previously treated with fluoropyrimidine- or platinum-containing chemotherapy.
REGARD was the first phase III study to show improved overall survival (OS) and progression-free survival (PFS) with a biologic agent in advanced gastric cancer after prior chemotherapy.
The results demonstrated that ramucirumab (8 mg/kg by infusion every 2 weeks) plus best supportive care (BSC), compared with placebo plus BSC, increased the median OS of patients with advanced gastric cancer by 37% (median OS of 5.2 months for ramucirumab vs. 3.8 months for placebo; hazard ratio [HR], 0.78; P = 0.047). In addition, ramucirumab significantly improved PFS, demonstrating a 62% increase in median PFS (2.1 months for ramucirumab vs. 1.3 months for placebo; HR, 0.48; P
Gastric cancer is the fifth most common cancer in the world and is the third leading cause of cancer death. Nearly one million new cases occurred worldwide in 2012 (631,000 men and 320,000 women), with approximately 723,000 deaths (469,000 men and 254,000 women). Stomach cancer is more prevalent in countries outside the U.S. and E.U. In the U.S., it is estimated that approximately 22,000 people will be diagnosed with gastric cancer in 2014.
The labeling for Cyramza (ramucirumab) includes a boxed warning regarding an increased risk of hemorrhage, including severe and sometimes fatal events. Cyranza should be discontinued in patients who experience severe bleeding. The most common adverse events (all grades) in the REGARD trial were hypertension (16% for ramucirumab vs. 8% for placebo), diarrhea (14% vs. 9%), headache (9% vs. 3%), and hyponatremia (6% vs. 2%). The most common serious AEs with ramucirumab were anemia (3.8%) and intestinal obstruction (2.1%).
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 involves the migration, growth, and differentiation of endothelial cells, which line the inside wall of blood vessels. Chemical signals in the body stimulate the repair of damaged blood vessels and the formation of new blood vessels during this process. In a person with cancer, angiogenesis creates new blood vessels that give a tumor its own blood supply, allowing it to grow and spread. Some tumors create VEGF proteins. These proteins attach to the VEGF receptors of blood vessel cells, causing new blood vessels to form around the tumors, enabling growth. Blocking the VEGF protein from linking to blood vessels helps to inhibit tumor growth by slowing angiogenesis and the blood supply that feeds tumors. Of the three known VEGF receptors, VEGF receptor 2 is linked most closely to VEGF-induced tumor angiogenesis.
Source: Eli Lilly; April 21, 2014.