The new angiogenesis inhibitor Ramucirumab (Cyramza, Eli Lilly and Company) was recently approved by the US FDA for the treatment of colorectal cancer, becoming another new indication for the drug. Ramucirumab is now approved in combination with the FOLFIRI regimen (folinic acid, fluorouracil, irinotecan) for the treatment of patients with metastatic colorectal cancer who develop disease progression during or after treatment with bevacizumab (Avastin, Genentech) in combination with oxaliplatin (Lexapro, Sanofi Aventis) + fluoropyrimidine. Ramucirumab was first approved in April 2014 as a single agent or in combination with paclitaxel for the treatment of patients with progressive or metastatic gastric cancer. in November 2014, its indication was extended to the treatment of adenocarcinoma of the esophagogastric junction. In December 2014, Ramucirumab was also approved in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer whose disease has progressed during or after platinum-based chemotherapy. In a statement, Dr. Sue Mahony, senior vice president and president of Lilly Oncology at Eli Lilly and Company, noted that FDA approval for all four indications of Ramucirumab was completed in just one year. Ramucirumab is an antagonist of vascular endothelial growth factor receptor 2 (VEGFR2) and is considered another effective agent after bevacizumab. The current FDA approval of Ramucirumab in colorectal cancer is based on the results of the RAISE study, a phase III clinical study comparing patients with progressive metastatic colorectal cancer treated with Ramucirumab in combination with the FOLFIRI regimen and placebo in combination with the FOLFIRI regimen after prior treatment. A total of 1072 patients were enrolled in the study and randomized in a 1:1 ratio to treatment with Ramucirumab in combination with the FOLFIRI regimen or placebo in combination with the FOLFIRI regimen. All patients enrolled were patients who had failed first-line bevacizumab in combination with other standard regimens of chemotherapy (oxaliplatin in combination with fluorouracil). Enrolled patients received intravenous 8 mg/kg of Ramucirumab or placebo every 2 weeks until disease progression, intolerable side effects, or patient death. The study’s primary study endpoint was overall survival. The study results showed that patients in the Ramucirumab-treated group had better median overall survival than those in the placebo-treated group (13.3 months vs. 11.7 months, P=0.0219), with a risk ratio (HR) of 0.84 in the Ramucirumab-treated group, suggesting that Ramucirumab combined with chemotherapy regimens reduced the risk of patient death by 16%. Patients in the Ramucirumab-treated group also had better progression-free survival than those in the placebo-treated group (5.7 months vs. 4.5 months, P=0.0005), with a 21% lower risk of disease progression (HR=0.79). In addition, Ramucirumab in combination with FOLFIRI was found to have more severe side effects than placebo in combination with FOLFIRI, with a higher incidence of grade 3 or higher side effects, including neutropenia (38.4% vs. 23.3%), hypertension (11.2% vs. 2.8%) and diarrhea (10.8% vs. 9.7%). Ramucirumab’s labeled side effects also included bleeding, gastrointestinal perforation, and interference with wound healing.