Panitumumab (INN), formerly ABX-EGF , is a fully human monoclonal antibody specific to the epidermal growth factor receptor (also known as EGF receptor , < i> EGFR , ErbB-1 and HER1 in humans).
Panitumumab is produced by Amgen and marketed as Vectibix . It was originally developed by Abgenix Inc.
In 2014, Amgen and Illumina entered into an agreement to develop a companion diagnosis to accompany the panitumumab.
Video Panitumumab
Usage
It was approved by the US Food and Drug Administration (FDA) for the first time in September 2006, for "EGFR treatment-expressing metastatic colorectal cancer with disease progression" despite prior treatment. Panitumumab was approved by the European Medicines Agency (EMEA) in 2007, and by Health Canada in 2008 for "treatment of colorectal cancer of EGFR refractory metastases in patients with non-wild-type KRAS".
Panitumumab was the first monoclonal antibody that demonstrated the use of KRAS as a predictive biomarker.
Maps Panitumumab
FDA Approval
Panitumumab was initially approved on 27 September 2006 for EGFR-expressing, metastatic CRC with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan regimens, based on results of studies showing clinical benefit in patients with metastatic colorectal cancer. In July 2009, the FDA updated the label of two anti-EGFR monoclonal antibody drugs (panitumumab and cetuximab) indicated for the treatment of metastatic colorectal cancer to include information about KRAS mutations. This is the result of a study, showing a lack of benefit with Panitumumab in patients carrying NRAS mutations.
It is also approved as a first-line agent in combination with FOLFOX.
Mechanism
Panitumumab is a human IgG2 monoclonal antibody.
EGFR is a transmembrane protein. Panitumumab works by binding to the EGFR extracellular domain that prevents activation. This results in inhibition of intracellular signal flow dependent on these receptors.
Pharmacokinetics
Pharmacokinetics (PK) panitumumab shows what is called target-mediated disposition behavior. However, PK is approximately linear in clinical doses, and terminal half-life for typical 80-kg and 60-year-old male patients with colorectal cancer is approximately 9.4 days.
Adverse Effects
Panitumumab has been linked to skin rashes, fatigue, nausea, diarrhea, fever, and decreased magnesium levels. Often, skin rashes are recorded in areas exposed to sunlight, such as the face or chest. Oral antibiotics may be necessary for worsening of skin rashes, such as those accompanied by abrasions and ulcers. Otherwise, topical steroid creams such as hydrocortisone may be helpful.
Ocular toxicity or keratitis is observed in 16% of patients on panitumumab, usually requiring treatment discontinuation.
In clinical trials, 90% of patients had dermatological toxicity and 15% of them were severe. Because of this, the panitumumab has a warning box warning alerting the patient. Skin toxicity usually appears two weeks after starting treatment. The more severe skin toxicity is associated with increased overall survival and overall survival.
Pulmonary fibrosis and interstitial lung disease were observed in clinical trials.
Contraindications
Panitumumab does not work in patients who have KRAS or NRAS mutations.
History
Panitumumab was produced using Abgenix's XenMouse platform technology, in which engineered mice were used to produce human antibodies. Abgenix partnered with Immunex Corporation to develop antibodies, and Amgen acquired Immunex in 2003. In 2006, Amgen acquired Abgenix as well. In 2013, Amgen formed an agreement with Zhejiang Beta Pharma to form Amgen Beta Pharmaceuticals and market the panitumumab in China. Amgen and Takeda have an agreement in which Takeda will develop and commercialize the panitumumab in Japan. Panitumumab is licensed to Dr Reddys Laboratories in India and GlaxoSmithKline in the UK.
Research
Pantiumumab is being studied in various phase II and III clinical trials. Phase III clinical trials include treatment of esophageal cancer, urotelial carcinoma, head and neck cancer metastasis, and liver metastasis in colorectal cancer. Early trials showed limited efficacy in patients with malignant melanoma, bladder cancer, prostate cancer, and renal cell carcinoma.
Panitumumab vs. Cetuximab
Although both target EGFR, panitumumab (IgG2) and cetuximab (IgG1) differ in their isotype and they may differ in their mechanism of action. The monoclonal antibody of IgG1 isotype may activate complement pathways and mediate cellular dependent cellular antibody (ADCC) cytotoxicity. It is unclear at this time, if one drug is superior to the other. In one study, both drugs were noted similarly in activity.
References
Further reading
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Amado, Rafael G.; Wolf, Michael; Peeters, Marc; Van Cutsem, Eric; Siena, Salvatore; Freeman, Daniel J.; Juan, Todd; Sikorski, Robert; Suggs, Sid; Radinsky, Robert; Patterson, Scott D.; Chang, David D. (2008). "Wild-Type Required for Effectiveness of Panitumumab in Patients with Metastatic Colorectal Cancer". Journal of Clinical Oncology . 26 (10): 1626-34. doi: 10.1200/JCO.2007.14.7116. PMIDÃ, 18316791 - Van Cutsem, Eric; Peeters, Marc; Siena, Salvatore; Humblet, Yves; Hendlisz, Alain; Neyns, Bart; Canon, Jean-Luc; Van Laethem, Jean-Luc; Maurel, Joan; Richardson, Gary; Wolf, Michael; Amado, Rafael G. (2007). "Open-Labels Phase III Trial Panitumumab Plus Best Supporting Treatment Compared to Self-Supporting Care in Patients with Chemotherapy-Refractory Metastatic Colorectal Cancer". Journal of Clinical Oncology . 25 (13): 1658-64. doi: 10.1200/JCO.2006.08.1620. PMIDÃ, 17470858
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