Cyramza by Eli Lilly

Cyramza (ramucirumab) was approved for treatment of patients with advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma after disease progression.

On April 21, 2014, the FDA announced approval of Cyramza (ramucirumab)¹ for use as a single-agent treatment in patients with advanced or metastatic gastric cancer, or in patients with gastroesophageal junction adenocarcinoma after disease progression following initial use of fluoropyrimidine- or platinum-based chemotherapy. Cyramza carries a black box warning for hemorrhage, including potentially fatal hemorrhagic events. In patients who experience severe bleeding while taking Cyramza, treatment should be discontinued.²

Mechanism of Action

Cyramza binds specifically to the vascular endothelial growth factor receptor 2 (VEGFR2) receptor, blocking activation of the VEGFR2 receptor, and preventing proliferation and migration of endothelial cells.²

Dosage and Administration

Each 10-mL or 50-mL single-dose vial of Cyramza contains ramucirumab at a concentration of 10 mg/mL in a sterile, preservative-free solution. Before preparation, vials should be stored in a refrigerator at a temperature between 36°F and 46°F. Vials of Cyramza should not be removed from the carton until preparation to protect the active ingredient from light.²

To prepare Cyramza, first, vials of medication should be inspected for discoloration and particulate matter. Discolored solutions or solutions that contain particulates should be discarded. The required dose of Cyramza should be diluted with isotonic saline solution to a final volume of 250 mL. To ensure adequate mixing, the solution should be inverted gently, but should not be shaken.²

After preparation with isotonic saline solution, the prepared solution of Cyramza remains stable for up to 4 hours at room temperature (below 77°F) and for up to 24 hours when stored under refrigeration (36°F to 46°F).²

To reduce the risk of an allergic reaction, patients should receive treatment with an intravenous antihistamine before receiving an infusion of Cyramza. The recommended dose of Cyramza is 8 mg/kg of medication administered intravenously every 2 weeks over a 60-minute infusion period, although as detailed in the package insert, this dose may require adjustment to manage adverse events and patient-specific concerns.²

Clinical Trials

Cyramza was evaluated in the double-blind, randomized, multinational, phase III REGARD trial. Of 355 patients with gastric cancer, patients received either Cyramza (at a dose of 8 mg/kg, every 2 weeks) plus best supportive care, or placebo plus best supportive care, in an approximately 2:1 ratio.³

Patients enrolled in the trial had experienced metastatic gastric cancer or locally advanced gastric cancer and were previously treated with a first-line therapy or with an adjuvant therapy. Per inclusion criteria, progression of gastric cancer had occurred within 4 months of receiving the last dose of a first-line therapy for gastric cancer or within 6 months of receiving the last dose of an adjuvant therapy for gastric cancer. In addition, patient performance status was required to be either 0 or 1 on the Eastern Cooperative Oncology Group performance status scale.³

Patients receiving Cyramza survived a median of 5.2 months (95% confidence interval [CI]: 4.4-5.7), significantly longer (P <.047) than patients receiving placebo who survived a median of 3.8 months (95% CI: 2.8-4.7). Progression-free survival was 2.1 months (95% CI: 1.5-2.7) for patients receiving Cyramza versus 1.3 months (95% CI: 1.3-1.4) for patients receiving placebo, which is a statistically significant difference (P <.001).³

Warnings and Precautions

Although formal drug interactions studies with Cyramza have not been conducted, patients taking nonsteroidal anti-inflammatory drugs were excluded from the REGARD trial.²

Cyramza is a Pregnancy Category C medication. Scientists have observed embryofetal abnormalities in animal models in which VEGF signaling has been disrupted, but no studies have evaluated the specific effects of Cyramza in animal models.²

Important warnings and precautions include an increased risk of hemorrhage, an increased risk of arterial thromboembolic events (including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischemia), gastrointestinal perforation, hypertension (blood pressure should be checked every 2 weeks during treatment), and reversible posterior leukoencephalopathy syndrome.²

Infusion-related reactions, with symptoms including chest pain or tightness, chills, wheezing, and paraesthesia, have occurred in clinical trials. During infusion of Cyramza, equipment for management of severe infusion-related reactions, such as bronchospasm, supraventricular tachycardia, and hypotension, should be readily available.²

Cyramza should be discontinued permanently in patients who experience grade-3 or -4 infusion-related reactions. Cyramza may also require discontinuation due to impaired wound healing or deterioration of liver function in patients with Child-Pugh class B or C cirrhosis.² For a complete discussion of potential adverse events and drug interactions with Cyramza, please consult the product package insert. SPT

References

• FDA approves Cyramza for stomach cancer. FDA website. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394107.htm. Accessed May 2014.
• Cyramza (ramucirumab) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2014.
• Fuchs CS, Tomasek J, Yong CJ, et al; for REGARD trial investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31-39.

About the Author

Michael R. Page, PharmD, RPh, earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.