On April 21, 2014, the U. S. Food and Drug Administration approved ramucirumab (Cyramza, Eli Lilly and Company) for use as a single agent for the treatment of patients with advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior treatment with fluoropyrimidine- or platinum-containing chemotherapy. Ramucirumab is a recombinant monoclonal antibody of the IgG1 class that binds to vascular endothelial growth factor receptor-2 (VEGFR-2) and blocks the activation of the receptor.
This approval was based on the demonstration of improved overall survival (OS) in a multinational, randomized (2:1), double-blind, multicenter study (I4T-IE-JVBD) enrolling 355 patients with previously treated advanced or metastatic, gastric or GEJ adenocarcinoma. Patients enrolled in Study I4T-IE-JVBD were randomized to receive either ramucirumab plus best supportive care (BSC) or placebo plus BSC.
In Study I4T-IE-JVBD, the median overall survival was 5.2 months in the ramucirumab plus BSC arm and 3.8 months in the placebo plus BSC arm [HR 0.78 (95% CI: 0.60, 0.998), p =0.047, stratified log rank test]. Median progression-free survival was longer in the ramucirumab arm compared to the placebo arm [HR 0.48 (95% CI: 0.38, 0.62), p <0.001, stratified log rank test].
The safety of ramucirumab as a single agent was evaluated in 570 patients, including 236 patients with locally advanced or metastatic gastric or GEJ adenocarcinoma, with an ECOG performance status of less than or equal to 1, who received ramucirumab in Study I4T-IE-JVBD. The most common adverse reactions (all grades) observed in ramucirumab-treated patients at a rate of greater than or equal to 10% and greater than or equal to 2% higher than placebo were hypertension and diarrhea. The grade 3-4 adverse reactions reported at a higher incidence in the ramucirumab arm (greater than or equal to2% difference between arms) included hypertension and hyponatremia. The most common serious adverse events with ramucirumab were intestinal obstruction (2.1%) and anemia (3.8%). Other important risks described in labeling include hemorrhage, arterial thrombotic events, infusion-related reactions, gastrointestinal perforation, impaired wound healing, clinical deterioration in patients with cirrhosis, and reversible posterior leukoencephalopathy.
The sponsor recently reported the findings of Study I4T-IE-JVBE, a multi-national, randomized (1:1), placebo-controlled study enrolling 665 patients with previously treated advanced or metastatic, gastric or GEJ adenocarcinoma, in which patients received either paclitaxel plus placebo or paclitaxel plus ramucirumab. This trial was reported to demonstrate a survival advantage for the ramucirumab combination.
The recommended ramucirumab dose and schedule is 8 mg/kg administered as a 60-minute intravenous infusion every 2 weeks.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125477lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm
by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).