General Information

Cyramza (ramucirumab) is a human VEGFR2 antagonist and it is a recombinant human IgG1 monoclonal antibody.

Cyramza is specifically indicated in combination with FOLFIRI (irinotecan, folinic acid, and fluorouracil) for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

Cyramza is supplied as an injection for intravenous administration. Prior to each Cyramza infusion, premedicate all patients with an intravenous histamine-1 receptor antagonist (e.g., diphenhydramine hydrochloride). For patients who have experienced a Grade 1 or 2 IRR, premedicate with a histamine-1 receptor antagonist, dexamethasone (or equivalent), and acetaminophen prior to each Cyramzainfusion. The recommended dosage of Cyramza is 8 mg/kg every 2 weeks administered by intravenous infusion over 60 minutes prior to FOLFIRI administration. Continue Cyramza until disease progression or unacceptable toxicity. Refer to the prescribing information for fluorouracil, leucovorin, and irinotecan for dosage information.

Clinical Results

FDA Approval

The FDA approval of Cyramza for colorectal cancer was based on the phase 3 global, double-blind RAISE study of Cyramza plus FOLFIRI compared to placebo plus FOLFIRI as a second-line treatment for mCRC in patients who had disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Patients were randomized in a 1:1 ratio to receive Cyramza plus FOLFIRI (n=536) or placebo plus FOLFIRI (n=536) every two weeks. In the RAISE trial, patients treated with the Cyramza-FOLFIRI combination achieved a median OS, the study's primary endpoint, of 13.3 months as compared to those treated with placebo-FOLFIRI who achieved 11.7 months, a statistically significant improvement that reduced the risk of patient death by 15 percent. The percentage of deaths at the time of analysis was 69 percent (372 patients) and 74 percent (397 patients) in the Cyramza-plus-FOLFIRI and placebo-plus-FOLFIRI treatment arms, respectively.

Side Effects

Adverse effects associated with the use of Cyramza plus FOLFIRI may include, but are not limited to, the following:

diarrhea

neutropenia

decreased appetite

epistaxis

stomatitis

The most common serious adverse events with Cyramza plus FOLFIRI were diarrhea, intestinal obstruction and febrile neutropenia.

Mechanism of Action

Cyramza (ramucirumab) is a human VEGFR2 antagonist and it is a recombinant human IgG1 monoclonal antibody. Cyramza specifically binds VEGFR2 and blocks binding of VEGFR ligands, VEGF-A, VEGF-C, and VEGF-D. As a result, ramucirumab inhibits ligand-stimulated activation of VEGFR2, thereby inhibiting ligand-induced proliferation, and migration of human endothelial cells.

Additional Information

For additional information regarding Cyramza or metastatic colorectal cancer, please visit the Cyramza web page.