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 docetaxel for the treatment of 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 Cyramza.

Cyramza is specifically indicated for use in combination with erlotinib, for the first-line treatment of patients with metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.

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 Cyramza infusion. The recommended dose of Cyramza for non-small cell lung cancer is 10 mg/kg administered by intravenous infusion over 60 minutes on day 1 of a 21-day cycle prior to docetaxel infusion. Continue Cyramza until disease progression or unacceptable toxicity. Refer to the prescribing information for docetaxel for dosage information.

Clinical Results

FDA Approval

The FDA approval of Cyramza for non-small cell lung cancer was based on the phase 3 REVEL trial. The trial enrolled 1253 patients with mostly non-squamous stage 4 disease, but did include about a quarter of patients with squamous carcinoma. Patients were given either docetaxel in combination with placebo or 10 mg/kg of Cyramza on day 1 of a three-week cycle. Patients were treated until disease progression or unacceptable toxicity. Data which showed a 1.4-month improvement in overall survival (OS) when comparing the combination with docetaxel alone. Median OS was 10.5 months in the combination arm compared with 9.1 months in the docetaxel-alone arm. Progression-free survival (PFS) was also improved with the combination: Median PFS was 4.5 months with the combination and 3 months with docetaxel alone.

The FDA approval of Cyramza for use in combination with erlotinib, for the first-line treatment of patients with metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations was based on the global, randomized, placebo-controlled Phase 3 RELAY trial. In the RELAY study, Cyramza in combination with erlotinib, a globally approved EGFR-targeting tyrosine kinase inhibitor (TKI), demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) – the time patients lived without their cancer growing or spreading after starting treatment – compared to placebo in combination with erlotinib [19.4 months in the Cyramza-containing arm compared to 12.4 months in the placebo-containing arm. The PFS treatment effect was consistent across exon 19 and exon 21 subgroups.

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.