Ramucirumab Is Approved for the Treatment of Advanced Gastric Cancer

By now we are all familiar with vascular endothelial growth factor (VEGF) and its role in tumor growth.  Bevacizumab (Avastin), a well-known VEGF inhibitor, is a monoclonal antibody widely utilized in the treatment of various cancers, often in combination with other chemotherapeutic agents.  Bevacizumab works by binding to VEGF receptors on the surface of endothelial cells, thereby blocking angiogenic activity. But now there's a new drug in town: ramucirumab.

Ramucirumab (Cyramza), approved in April 2014, is a VEGF Receptor 2 (VEGF2) inhibitor indicated for patients with advanced/metastatic gastric or gastroesophageal junction adenocarcinoma with disease progression on or after 5-FU or platinum-based therapy.  There are many similarities between bevacizumab and ramucirumab, which may aid you as a clinician in understanding the drug. There are also a few unique additions to consider as well.

Ramucirumab is administered IV every 2 weeks over 60 minutes. You must premedicate with an IV H1 antagonist (e.g., diphenhydramine) due to the risk of a hypersensitivity reaction. In our practice, we are also giving IV famotidine with the first two treatments (i.e., cycle 1). Per the package insert (PI), if a patient has a grade 1 or 2 reaction, it is recommended to add IV dexamethasone for future administration.

The most commonly reported side effects with ramucirumab include hypertension (16%), diarrhea (14%), and anemia (11%).  In clinical trials, 16% of patients had an infusion reaction. There is also the risk of proteinuria; thus a urine sample should be obtained prior to each infusion. Dose reduction guidelines exist in the PI if proteinuria becomes an issue.

Lesser reported side effects include headache, rash, epistaxis, intestinal obstruction, and neutropenia. Like bevacizumab, there is the rare potential for arterial thrombosis, bowel perforation, and hemorrhage on ramucirumab. You may also see delayed wound healing and thus it is important to consider its administration in relation to recent or upcoming surgeries or invasive procedures.

We currently have three patients who have received treatment with ramucirumab. Two have newly started after progressing on a previous regimen of carboplatin/paclitaxel, and then more recently capecitabine. Both have roughly two treatments (1 cycle) under their belts and thus far are having no treatment-related issues per se.  The third patient received three treatments, however with cycle 2, day 15 therapy was held due to severe hypertension (i.e., systolic >200). This patient has baseline hypertension and was referred back to his PCP.  Despite adjustments to his medications, the patient continued with erratic blood pressures and severe headaches. We therefore held further treatment and pursued repeat scans to assess response. Unfortunately, he has had widespread progression and is now considering further chemotherapy versus palliative measures only.

Have you seen this drug used in clinical practice? What has been your experience with patient tolerance and side effects? Are you noting a response to therapy?