Ramucirumab

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Ramucirumab
Monoclonal antibody
Type Whole antibody
Source Human
Target VEGFR2 (KDR)
Clinical data
Trade names Cyramza
AHFS/Drugs.com cyramza
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration
Intravenous infusion
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Probably proteases
Biological half-life 14 days
Identifiers
CAS Number
ChemSpider
  • none
UNII
Chemical and physical data
Formula C6374H9864N1692O1996S46
Molar mass 143.6 kg/mol
 NYesY (what is this?)  (verify)

Ramucirumab[1] (LY3009806, IMC-1121B, trade name Cyramza[2][3]) is a fully human monoclonal antibody (IgG1) developed for the treatment of solid tumors. This drug was developed by ImClone Systems Inc. It was isolated from a native phage display library from Dyax.

Approved uses[edit]

On 21 April 2014, the US Food and Drug Administration (FDA) approved ramucirumab, as a single agent or with paclitaxel, for treatment of advanced gastric or gastro-esophageal junction adenocarcinoma if the disease has progressed despite fluoropyrimidine- or platinum-containing chemotherapy.[4][5]

On 12 December 2014, the FDA approved ramucirumab in combination with docetaxel, for treatment of metastatic non-small-cell lung carcinoma (NSCLC) with disease progression on or after platinum-containing chemotherapy. If the cancer has a sensitizing mutation of EGFR or ALK previous therapy should have included targeted therapy for the genomic tumor aberration.[6]

In Europe, the drug is approved since 21 January 2015 for gastric or gastro-esophageal junction cancer under the same conditions. Meanwhile, it has also been approved for NSCLC, as well as in combination with FOLFIRI for the treatment of metastatic colorectal cancer if the disease has progressed despite bevacizumab, oxaliplatin and capecitabine (or sililar) therapy.[7][8]

Contraindications[edit]

Under the European approval, NSCLC therapy with ramucirumab is contraindicated when there is tumour cavitation, or if major vessels are involved.[7][9]

Side effects[edit]

The most common adverse effects in a study investigating ramucirumab monotherapy were diarrhoea (14% of patients, as compared to 9% under placebo), hyponatraemia (low blood sodium levels; 6% versus 2%), headache (9% versus 3%), and high blood pressure (16% versus 8%).[10]

Interactions[edit]

In studies, no interactions were observed with paclitaxel, docetaxel or irinotecan.[7][10]

Pharmacology[edit]

Mechanism of action[edit]

It is directed against the vascular endothelial growth factor receptor 2 (VEGFR2). By binding to VEGFR2 it works as a receptor antagonist blocking the binding of vascular endothelial growth factor (VEGF) to VEGFR2. VEGFR2 is known to mediate the majority of the downstream effects of VEGF in angiogenesis.[11]

Clinical trials[edit]

On September 26, 2013 the manufacturer Eli Lilly announced that its Phase III study for ramucirumab failed to hit its primary endpoint on progression-free survival among women with metastatic breast cancer.[12][13]

In June 2014, a phase III trial of the drug reported it failed to improve overall survival in liver cancer.[14]

In Feb 2016 it was reported that a phase II trial of adding ramucirumab to docetaxel improved progression-free survival (PFS) compared with docetaxel alone in locally advanced or metastatic urothelial carcinoma.[15] It is now in the RANGE phase III trial for this indication.[16]

References[edit]