Panitumumab
Monoclonal antibody | |
---|---|
Type | Whole antibody |
Source | Human |
Target | Epidermal growth factor receptor (EGFR) |
Clinical data | |
Trade names | Vectibix |
Other names | ABX-EGF |
AHFS/Drugs.com | Monograph |
MedlinePlus | a607066 |
License data |
|
Intravenous | |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Elimination half-life | ~9.4 days (range: 4-11 days) |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
|
UNII | |
KEGG | |
ChEMBL | |
PDB ligand | |
Chemical and physical data | |
Formula | C6398H9878N1694O2016S48 |
Molar mass | 144324.12 g·mol−1 |
(what is this?) (verify) |
Panitumumab, sold under the brand name Vectibix, is a fully human monoclonal antibody specific to the epidermal growth factor receptor (also known as EGF receptor, EGFR, ErbB-1 and HER1 in humans).[2][3]
Panitumumab is manufactured by Amgen and was originally developed by Abgenix Inc.
In 2014, Amgen and
Medical uses
Panitumumab was approved by the U.S. Food and Drug Administration (FDA) for the first time in September 2006, for "the treatment of EGFR-expressing metastatic colorectal cancer with disease progression" despite prior treatment.[5] Panitumumab was approved by the European Medicines Agency (EMEA) in 2007, and by Health Canada in 2008, for "the treatment of refractory EGFR-expressing metastatic colorectal cancer in patients with non-mutated (wild-type) KRAS".
Panitumumab was the first monoclonal antibody to demonstrate the use of KRAS as a predictive biomarker.
Contraindications
Panitumumab does not work in patients who have KRAS or NRAS mutations.[6]
Adverse effects
Panitumumab has been associated with skin rash, fatigue, nausea, diarrhea, fever, and decreased magnesium levels. Often, skin rash is noted in the sun exposed parts of the body, such as the face or chest. Oral antibiotics may be needed for worsening skin rash, such as one accompanied with blisters and ulcers. Otherwise, topical steroid creams like hydrocortisone may help.[7]
Ocular toxicity or keratitis was observed in 16% of patients on panitumumab, usually necessitating the discontinuance of therapy.[8]
In clinical trials, 90% of patients had dermatological toxicities and 15% of those were severe. Because of this, panitumumab has a boxed warning cautioning patients. Skin toxicities were typically apparent two weeks after beginning treatment. More severe skin toxicities were associated with improved progression free survival and overall survival.[8]
Pulmonary fibrosis and interstitial lung disease were observed in clinical trials.[8]
Pharmacology
Mechanism of action
EGFR is a transmembrane protein. Panitumumab works by binding to the extracellular domain of the EGFR preventing its activation. This results in halting of the cascade of intracellular signals dependent on this receptor.[9]
Pharmacokinetics
The pharmacokinetics (PK) of panitumumab shows the so-called target-mediated disposition behavior.[10] However, the pharmacokinetics is approximately linear at clinical doses, and the terminal half-life for a typical male patient of 80 kg and 60 years of age with colorectal cancer is about 9.4 days.[medical citation needed]
History
Panitumumab was generated using
FDA approval
Panitumumab was initially approved on September 27, 2006, for EGFR-expressing, metastatic CRC with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens, based on the results of a study which showed clinical benefit in metastatic colorectal cancer patients.
It is also approved as a first-line agent in combination with FOLFOX.[8]
Research
Panitumumab is being studied in numerous phase II and III clinical trials. Phase III clinical trials include treatment of esophageal cancer,[14] urothelial carcinoma,[15] metastatic head and neck cancer,[16] and liver metastasis in colorectal cancer.[17] Early trials showed limited efficacy in patients with malignant melanoma, bladder cancer, prostate cancer, and renal cell carcinoma.[11]
Panitumumab vs. cetuximab
Although they both target the EGFR, panitumumab (
References
- FDA. Retrieved 22 Oct 2023.
- ^ a b "Vectibix- panitumumab solution". DailyMed. 25 August 2021. Archived from the original on 6 April 2022. Retrieved 6 July 2022.
- ^ a b "Vectibix EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 13 August 2021. Retrieved 6 July 2022.
- Gen. Eng. Biotechnol. News (paper). Vol. 34, no. 4. February 15, 2014. p. 32. Archivedfrom the original on September 19, 2016. Retrieved December 2, 2014.
- ^ "Drug Approval Package: Vectibix NDA #125147". U.S. Food and Drug Administration (FDA). 29 May 2007. Archived from the original on 31 March 2021. Retrieved 6 July 2022.
- ^ S2CID 14556160.
- S2CID 30651519.
- ^ a b c d "UpToDate". Archived from the original on 2017-02-02. Retrieved 2017-01-27.
- ISBN 978-1-59392-033-3.[page needed]
- S2CID 25766549.
- ^ a b "Panitumumab - Amgen". AdisInsight. Archived from the original on 2017-11-03. Retrieved 2017-01-27.
- PMID 16796788.
- ^ "FDA updates Vectibix and Erbitux labels with KRAS testing info". 20 July 2009. Archived from the original on 3 March 2016. Retrieved 2 December 2014.[unreliable medical source?]
- ^ Clinical trial number NCT01627379 for "Cisplatin and 5-FU +/- Panitumumab for Patients With Nonresectable,Advanced or Metastatic Esophageal Squamous Cell Cancer" at ClinicalTrials.gov
- ^ Clinical trial number NCT00460265 NCT00460265 for "I-MVAC +/- Panitumumab as First-line Treatment of Advanced Urothelial Carcinoma Without H-Ras Nor K-Ras Mutations" at ClinicalTrials.gov
- ^ Clinical trial number NCT00460265 NCT00460265 for "Study of Panitumumab Efficacy in Patients With Recurrent and/or Metastatic Head and Neck Cancer" at ClinicalTrials.gov
- ^ Clinical trial number NCT02162563 for "Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases" at ClinicalTrials.gov
- ^ HealthValue: IgG1 & IgG2 Archived 2019-06-05 at the Wayback Machine[unreliable medical source?]
- PMID 24739896.
Further reading
- Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. (April 2008). "Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer" (PDF). Journal of Clinical Oncology. 26 (10): 1626–34. (PDF) from the original on 2021-10-17. Retrieved 2019-09-02.
- Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. (May 2007). "Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer". Journal of Clinical Oncology. 25 (13): 1658–64. PMID 17470858.
External links
- "Panitumumab". Drug Information Portal. U.S. National Library of Medicine.