On November 5, 2014, the U. S. Food and Drug Administration approved ramucirumab (Cyramza, Eli Lilly and Company) for use in combination with paclitaxel for the treatment of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Ramucirumab was approved in April, 2014 as a single agent for the treatment of patients with advanced gastric or GEJ adenocarcinoma refractory to or progressive following first-line therapy with platinum or fluoropyrimidine chemotherapy.
The approval of ramucirumab in combination with paclitaxel was based on the demonstration of improved overall survival (OS) in a multicenter, double-blind, placebo-controlled study (I4T-IE-JVBE) that enrolled 665 patients with previously-treated advanced or metastatic gastric or GEJ adenocarcinoma. Patients were randomized to receive either ramucirumab (8 mg/kg every two weeks) in combination with paclitaxel (80 mg/m2 once a week for 3 weeks of every 28-day cycle) (n=330) or matching placebo plus paclitaxel (n=335).
A statistically significant prolongation of OS was demonstrated [HR 0.81; (95% CI: 0.68, 0.96); p=0.017]; median OS was 9.6 and 7.4 months in the ramucirumab plus paclitaxel arm and placebo plus paclitaxel arm, respectively. Progression-free survival was also significantly longer for patients receiving ramucirumab plus paclitaxel [HR=0.64 (95% CI: 0.54, 0.75); p<0.001)]
Safety data was evaluated in 656 patients who received at least one dose of study drug. The most frequently reported adverse reactions with ramucirumab plus paclitaxel (incidence greater than or equal to 30%) were fatigue/asthenia, neutropenia, diarrhea, and epistaxis. The most common serious adverse reactions with ramucirumab plus paclitaxel were neutropenia and febrile neutropenia (3.7% and 2.4%, respectively).
The recommended dose and schedule for ramucirumab in combination with paclitaxel for advanced gastric or GEJ adenocarcinoma is ramucirumab 8 mg/kg intravenously administered every 2 weeks and paclitaxel 80 mg/m2 intravenously once a week for 3 weeks of every 28-day cycle. Treatment should continue until disease progression or unacceptable toxicity.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125477s002lbl.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).