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 metastaticcolorectal cancer with disease progression" despite prior treatment.[4] Panitumumab was approved by theEuropean Medicines Agency (EMEA) in 2007, and byHealth 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 predictivebiomarker.
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.[6]
Ocular toxicity orkeratitis was observed in 16% of patients on panitumumab, usually necessitating the discontinuance of therapy.[7]
In clinical trials, 90% of patients had dermatological toxicities and 15% of those were severe. Because of this, panitumumab has aboxed 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.[7]
Pulmonary fibrosis and interstitial lung disease were observed in clinical trials.[7]
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.[8]
Thepharmacokinetics (PK) of panitumumab shows the so-calledtarget-mediated disposition behavior.[9] 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]
Panitumumab was generated usingAbgenix's XenoMouse platform technology, in which engineered mice were utilized to produce human antibodies. Abgenix partnered with Immunex Corporation to develop the antibody, 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 panitumumab in China. Amgen and Takeda have an agreement under which Takeda will develop and commercialise panitumumab in Japan.[10] Panitumumab is licensed toDr. Reddy's Laboratories[11] in India andGlaxoSmithKline in the UK.[citation needed]
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.[12] In July 2009, the FDA updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab andcetuximab) indicated for the treatment of metastatic colorectal cancer to include information about KRAS mutations.[13] This was the result of a study, which demonstrated lack of benefit with Panitumumab in patients who carriedNRAS mutations.[5]
It is also approved as a first-line agent in combination withFOLFOX.[7]
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 melanoma, bladder cancer, prostate cancer, and renal cell carcinoma.[10]
Although they both target the EGFR, panitumumab (IgG2) and cetuximab (IgG1) differ in theirisotype and they might differ in their mechanism of action. Monoclonal antibodies of the IgG1 isotype may activate the complement pathway and mediateantibody-dependent cellular cytotoxicity (ADCC).[18] It is not clear at this time if one drug is superior to the other. In one of the studies, both these drugs were noted to be similar in activity.[19]
^Lacouture ME, Mitchell EP, Piperdi B, Pillai MV, Shearer H, Iannotti N, et al. (March 2010). "Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer".Journal of Clinical Oncology.28 (8):1351–7.doi:10.1200/JCO.2008.21.7828.PMID20142600.S2CID30651519.
^Plunkett, Jack W. (September 30, 2005).Plunkett's Biotech & Genetics Industry Almanac 2006. Plunkett Research.ISBN978-1-59392-033-3.[page needed]
^Ma P, Yang BB, Wang YM, Peterson M, Narayanan A, Sutjandra L, et al. (October 2009). "Population pharmacokinetic analysis of panitumumab in patients with advanced solid tumors".Journal of Clinical Pharmacology.49 (10):1142–56.doi:10.1177/0091270009344989.PMID19723673.S2CID25766549.
^Gibson TB, Ranganathan A, Grothey A (May 2006). "Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer".Clinical Colorectal Cancer.6 (1):29–31.doi:10.3816/CCC.2006.n.01.PMID16796788.
^Clinical trial numberNCT01627379 for "Cisplatin and 5-FU +/- Panitumumab for Patients With Nonresectable, Advanced or Metastatic Esophageal Squamous Cell Cancer" atClinicalTrials.gov
^Clinical trial numberNCT00460265 NCT00460265 for "I-MVAC +/- Panitumumab as First-line Treatment of Advanced Urothelial Carcinoma Without H-Ras Nor K-Ras Mutations" atClinicalTrials.gov
^Clinical trial numberNCT00460265 NCT00460265 for "Study of Panitumumab Efficacy in Patients With Recurrent and/or Metastatic Head and Neck Cancer" atClinicalTrials.gov
^Clinical trial numberNCT02162563 for "Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases" atClinicalTrials.gov
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.doi:10.1200/JCO.2006.08.1620.PMID17470858.
N
Y (what is this?) (verify)
