On December 12, 2014, the U. S. Food and Drug Administration approved ramucirumab (Cyramza Injection, Eli Lilly and Company) for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving ramucirumab. Ramucirumab was previously approved as a single agent and for use in combination with paclitaxel for the treatment of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma after disease progression on first line therapy.
The approval of ramucirumab in combination with docetaxel in NSCLC was based on the demonstration of improved overall survival (OS) in a multicenter, double-blind, placebo-controlled study (I4T-MC-JVBA) that enrolled 1253 patients with previously treated metastatic NSCLC. Patients were randomized to receive either ramucirumab (10 mg/kg every three weeks) in combination with docetaxel (75 mg/m2 every 3 weeks) on day 1 of a 21-day cycle (n=628) or matching placebo plus docetaxel (n=625).
A statistically significant prolongation of OS was demonstrated [HR 0.86; (95% CI: 0.75, 0.98); p=0.024]; median OS was 10.5 months in the ramucirumab plus docetaxel arm and 9.1 months in the placebo plus docetaxel arm. Progression-free survival was also significantly longer for patients receiving ramucirumab plus docetaxel [HR=0.76 (95% CI: 0.68, 0.86); p<0.001)].
Safety data was evaluated in 1245 patients who received at least one dose of study drug. The most frequently reported adverse reactions with ramucirumab plus docetaxel (incidence greater than or equal to 30%) were neutropenia, fatigue/asthenia, and stomatitis/mucosal inflammation. The most common serious adverse reactions with ramucirumab plus docetaxel were febrile neutropenia (14%), pneumonia (6%), and neutropenia (5%).
The recommended dose and schedule for ramucirumab in combination with docetaxel for NSCLC is ramucirumab 10 mg/kg intravenously and docetaxel 75 mg/m2 intravenously administered every 3 weeks.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125477s007lbl.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).