Ramucirumab

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Ramucirumab
Intravenous infusion
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismProbably proteases
Elimination half-life14 days
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
Chemical and physical data
FormulaC6374H9864N1692O1996S46
Molar mass143609.63 g·mol−1
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Ramucirumab

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.

Approved uses

In April 2014, the US

platinum-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.[6] This trial has been criticised for its use of a placebo control arm, which does not reflect standard of care in most Western countries.[7]

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.[8]

In December 2014, the FDA approved ramucirumab in combination with

platinum-containing chemotherapy. The approval was based on REVEL trial.[9]

In April 2015, ramucirumab was approved by FDA for the treatment of patients with metastatic

5-fluorouracil (FOLFIRI) to FOLFIRI alone.[10]

In May 2019, ramucirumab was approved by FDA as a single agent treatment for

overall 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.

Contraindications

Under the European approval, NSCLC therapy with ramucirumab is contraindicated when there is tumour

cavitation, or if major vessels are involved.[12][13]

Side effects

The most common adverse effects in a study investigating ramucirumab monotherapy were

hyponatraemia (low blood sodium levels; 6% versus 2%), headache (9% versus 3%), and high blood pressure (16% versus 8%).[14]

Interactions

In studies, no interactions were observed with paclitaxel, docetaxel, or irinotecan.[12][14]

Pharmacology

Mechanism of action

Ramucirumab is a direct

VEGF-D). These ligands are secreted by solid tumors to promote angiogenesis (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.[15]

Clinical trials

In September 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.[16][17]

In June 2014, a phase III trial of the drug reported it failed to improve

overall survival in liver cancer.[18]

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 metastatic

urothelial carcinoma.[19] It is now in the RANGE phase III trial for this indication.[20]

Between 2016 and 2018, 26 hospitals in Italy conducted a multicentre, randomised, double-blind, placebo-controlled, phase 2 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.[21]

References

  1. ^ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  2. ^ "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.
  3. ^ Statement On A Nonproprietary Name Adopted By The USAN Council - Ramucirumab, American Medical Association.
  4. ^ "FDA OKs Lilly's blockbuster hopeful ramucirumab for stomach cancer". FierceBiotech. 21 April 2014.
  5. ^ "Cyramza official website".
  6. S2CID 41960459
    .
  7. PMID 28386297
    .
  8. PMID 25240821
    .
  9. S2CID 5078660
    .
  10. doi:10.1200/jco.2015.33.3_suppl.512
    .
  11. ^ Research, Center for Drug Evaluation and (10 May 2019). "FDA approves ramucirumab for hepatocellular carcinoma". FDA.
  12. ^ a b "Cyramza: EPAR – Product Information" (PDF). European Medicines Agency. 21 January 2015.
  13. ^ Haberfeld, H, ed. (2017). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Cyramza 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung.
  14. ^ a b FDA Professional Drug Information on Cyramza.
  15. ^ Ramucirumab (Cyramza) package insert
  16. ^ Clinical trial number NCT00703326 for "Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer" at ClinicalTrials.gov
  17. ^ Carroll J (26 September 2013). "In another stinging setback, Eli Lilly's ramucirumab fails PhIII breast cancer study". Retrieved 27 September 2013.
  18. ^ Philippidis A. "Lilly's Cyramza Fails Phase III Trial in Liver Cancer". Genetic Engineering & Biotechnology News. Archived from the original on 9 April 2016. Retrieved 12 June 2014.
  19. ^ Levitan D (February 2016). "Added to Docetaxel Extends PFS in Urothelial Carcinoma". Cancer Network. Archived from the original on 2 March 2020. Retrieved 4 March 2016.
  20. ^ Clinical trial number NCT02426125 for "A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer (RANGE)" at ClinicalTrials.gov
  21. S2CID 237471286
    .
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