The U.S. Food and Drug Administration (FDA) has approved ramucirumab (Cyramza) 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 mutations should have experienced disease progression on FDA-approved therapy for these mutations prior to receiving ramucirumab.
This is the third indication that ramucirumab has received in 2014. 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 adenocarcinoma after disease progression on first-line therapy.
Clinical Study Details
The approval of ramucirumab in combination with docetaxel in NSCLC was based on the demonstration of improved overall survival in a multicenter, double-blind, placebo-controlled study (I4T-MC-JVBA) that enrolled 1,253 patients with previously treated metastatic NSCLC. Patients were randomly assigned to receive either ramucirumab (10 mg/kg every 3 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 overall survival was demonstrated (hazard ratio [HR] = 0.86, 95% confidence interval = 0.75–0.98, P = .024); median overall survival 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 < .001).
Safety data were evaluated in 1,245 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%). ■