| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | VEGFR2 (KDR) |
| Clinical data | |
| Trade names | Cyramza |
| Other names | LY3009806, IMC-1121B |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a614026 |
| License data | |
| Routes of administration | Intravenous infusion |
| Drug class | Antineoplastic agents |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Metabolism | Probablyproteases |
| Eliminationhalf-life | 14 days |
| Identifiers | |
| CAS Number | |
| DrugBank |
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| ChemSpider |
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| UNII | |
| Chemical and physical data | |
| Formula | C6374H9864N1692O1996S46 |
| Molar mass | 143609.63 g·mol−1 |
 N Y (what is this?) (verify) | |
Ramucirumab([5]), sold under the brand nameCyramza, is a fully humanmonoclonal antibody (IgG1) used for the treatment of cancer.[3][4] Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist.[3][4] Ramucirumab was developed byImClone Systems.[not verified in body] It was isolated from a nativephage display library fromDyax.[not verified in body]
Ramucirumab isindicated for the treatment of gastric cancer, colorectal cancer, non-small cell lung cancer, and hepatocellular carcinoma.[3][4]
Under the European approval, NSCLC therapy with ramucirumab is contraindicated when there is tumourcavitation, or if major vessels are involved.[6][7]
The most common adverse effects in a study investigating ramucirumab monotherapy werediarrhea (14% of patients, as compared to 9% underplacebo),hyponatraemia (low bloodsodium levels; 6% versus 2%), headache (9% versus 3%), and high blood pressure (16% versus 8%).[3][4]
In studies, no interactions were observed withpaclitaxel,docetaxel, oririnotecan.[3][4][6]
Ramucirumab is a directVEGFR2 antagonist, that binds with high affinity to the extracellular domain of VEGFR2 and block the binding of natural VEGFR ligands (VEGF-A,VEGF-C andVEGF-D). These ligands are secreted by solid tumors to promoteangiogenesis (formation of new blood vessels from pre-existing ones) and enhance tumor blood supply. Binding of ramucirumab to VEGFR2 leads to inhibition of VEGF-mediated tumor angiogenesis.[8]
In April 2014, the USFood and Drug Administration (FDA) approved ramucirumab as a single-agent treatment for advancedgastric cancer or gastro-esophageal junction (GEJ)adenocarcinoma after prior treatment withfluoropyrimidine- orplatinum-containing chemotherapy. The approval was based on the results of the REGARD trial, a phase III, international, randomized, double-blind, placebo-controlled study, that evaluated the safety and efficacy of ramucirumab combinated with best supportive care versus placebo.[9] This trial has been criticised for its use of a placebo control arm, which does not reflect standard of care in most Western countries.[10]
Ramucirumab has also been studied in combination with paclitaxel (a type of chemotherapy) and received additional FDA approval on 5 November 2014 as a treatment for people with advanced gastric cancer or GEJ adenocarcinoma after prior treatment with fluoropyrimidine- or platinum-based chemotherapy. The approval was based on the results of the RAINBOW trial, that compared ramucirumab plus paclitaxel or paclitaxel alone.[11]
In December 2014, the FDA approved ramucirumab in combination withdocetaxel for treatment of metastaticnon-small-cell lung carcinoma (NSCLC) with disease progression during or after first-lineplatinum-containing chemotherapy. The approval was based on REVEL trial.[12]
In April 2015, ramucirumab was approved by FDA for the treatment of patients with metastaticcolorectal cancer (mCRC) with disease progression on or after prior therapy withbevacizumab,oxaliplatin, andfluoropyrimidine. The approval was based on the results of the RAISE trial, a phase III study, which compared ramucirumab plusirinotecan,folinic acid, and5-fluorouracil (FOLFIRI) to FOLFIRI alone.[13]
In May 2019, ramucirumab was approved by FDA as a single agent treatment forhepatocellular carcinoma (HCC) in patients who have analpha fetoprotein (AFP) of > 400 ng/mL and have been previously treated withsorafenib.[14] The approval was based on REACH-2 (NCT02435433), a multinational,randomized,double-blind,placebo-controlled, multicenter study in patients with advanced HCC with AFP > 400 ng/mL who had disease progression on or after sorafenib or who were intolerant. The estimated medianoverall survival (OS) was 8.5 months (7.0-10.6 months) for patients receiving ramucirumab and 7.3 months (5.4-9.1 months) for those receiving placebo.
In September 2013, the manufacturerEli Lilly announced that its phase III study for ramucirumab failed to hit its primary endpoint onprogression-free survival among women with metastaticbreast cancer.[15][16]
In June 2014, a phase III trial of the drug reported it failed to improveoverall survival inliver cancer.[17]
In February 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 metastaticurothelial carcinoma.[18] It is now in theRANGE phase III trial for this indication.[19]
Between 2016 and 2018, 26 hospitals in Italy conducted a multicentre, randomised, double-blind, placebo-controlled, phase II trial to evaluate the safety and effectiveness of the anti-VEGFR-2 antibody ramucirumab combined with gemcitabine in patients with pretreated pleural mesothelioma. Combining ramucirumab to standard second line gemcitabine significantly improved overall survival after failure of first-line chemotherapy, with a favourable safety profile.[20]
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