FDA Approves Ramucimurab (Cyramza) for the Treatment of Non-Small Cell Lung Cancer (NSCLC)

Posted by Dr. Guneet Walia on December 12th, 2014

The US Food and Drug Administration approved ramucimurab (Cyramza injection, Eli Lily) for use in combination with docetaxel for the treatment of patients with metastatic non small cell lung cancer with disease progression on or after platinum-based chemotherapy.

Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving ramucirumab.

Ramucimurab is a fully human monoclonal antibody that binds the Vascular Endothelial Growth Factor Receptor (VEGFR) and blocks its activation. The family of VEGFRs plays important roles in angiogenesis (formation of new blood vessels) as well as vasculogenesis (formation of the circulatory system).

Solid tumors cannot grow beyond a certain size without the formation of new blood vessels that can deliver oxygen and nutrients to the inner cells of the tumor, therefore cancers lay new blood vessels. Vascular Endothelial Growth Factors (VEGFs) and their receptors (VEGFRs) play important roles in this process of angiogenesis and therefore contribute to the growth and spread of cancer. The overexpression of these growth factors and their receptors is typically associated with poor disease prognosis.

Thus, both VEGFs and VEGFRs are important drug targets to stop cancer metastasis and progression. Inhibitors of VEGFs and VEGFRs bind to these proteins, preventing their interaction with their cognate binding partner.

Angiogenesis inhibitors are hypothesized to work best with chemotherapy agents as the former normalize blood vessels that supply the tumor, facilitating the delivery of the anticancer chemotherapeutics to the tumor core, thereby effecting maximal cell killing.

Ramucimurab was approved by the FDA earlier this year for the treatment of advanced gastric cancer (after disease progression on first line therapy), both as monotherapy as well as in combination with paclitaxel.

The FDA’s approval of ramucimurab today for the treatment of NSCLC is based off of the results from the REVEL study, an international phase III trial that studied the effects of the drug in 1253 patients with previously treated and progressive nonsquamous and squamous cell NSCLC from 26 countries on six continents. Patients were randomized to receive either ramucirumab (10 mg/kg every three 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). Treatment was provided till the development of disease progression or the development of intolerable side effects.

Ramucimurab showed a statistically significant prolongation of overall survival, demonstrating that patients on ramucimurab plus docetaxel survived an average of 10.5 months from the start of treatment, compared to an average of 9.1 months in patients on placebo plus docetaxel.

The overall response rate was also better in the ramucirumab plus docetaxel group (23% vs. 14%; P < .0001).

According to the manufacturer, the most common grade 3 and higher adverse events, which occurred more frequently in patients in the ramucirumab than in the placebo group, were neutropenia, i.e. an increase in the counts of infection-fighting white blood cells (48.8% vs. 39.8%), febrile neutropenia (15.9% vs. 10.0%), fatigue (14.0% vs. 10.5%), leukopenia (13.7% vs. 12.5%), and hypertension (5.6% vs. 2.1%). Grade 5 adverse events were comparable in the ramucirumab and placebo groups (5.4% vs. 5.8%).

Patients in the ramucirumab group experienced more bleeding/hemorrhage events of any grade than those in the placebo group (28.9% vs. 15.2%), but the rate of grade 3 or higher bleeding/hemorrhage events was similar in the two groups (2.4% vs. 2.3%). Ramucimurab can cause severe bleeding, blood clots, elevation in blood pressure and may impair wound healing.

Ramucimurab is marketed as Cyramza by Indianapolis-based Eli Lilly.

The FDA recommended dose and schedule for ramucirumab in combination with docetaxel for NSCLC is ramucirumab 10 mg/kg intravenously and docetaxel 75 mg/m2 intravenously administered every 3 weeks.

Full prescribing information is available here: Cyramza Prescribing Information

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