Panitumumab

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.{{cite web | title=Drug Approval Package: Vectibix NDA #125147 | website=U.S. Food and Drug Administration (FDA) | date=29 May 2007 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125147s0000TOC.cfm | access-date=6 July 2022 | archive-date=31 March 2021 | archive-url=https://web.archive.org/web/20210331092303/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125147s0000TOC.cfm | url-status=live }} 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.

Panitumumab does not work in patients who have KRAS or NRAS mutations.

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.{{cite journal | vauthors = Lacouture ME, Mitchell EP, Piperdi B, Pillai MV, Shearer H, Iannotti N, Xu F, Yassine M | display-authors = 6 | title = 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 = Journal of Clinical Oncology | volume = 28 | issue = 8 | pages = 1351–7 | date = March 2010 | pmid = 20142600 | doi = 10.1200/JCO.2008.21.7828 | s2cid = 30651519 }}

Ocular toxicity or keratitis was observed in 16% of patients on panitumumab, usually necessitating the discontinuance of therapy.

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.

Pulmonary fibrosis and interstitial lung disease were observed in clinical trials.

{{main|Epidermal growth factor receptor}}

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.{{cite book |first=Jack W. |last=Plunkett |title=Plunkett's Biotech & Genetics Industry Almanac 2006 | publisher=Plunkett Research | date=September 30, 2005 |isbn=978-1-59392-033-3 }}{{page needed|date=December 2014}}

The pharmacokinetics (PK) of panitumumab shows the so-called target-mediated disposition behavior.{{cite journal | vauthors = Ma P, Yang BB, Wang YM, Peterson M, Narayanan A, Sutjandra L, Rodriguez R, Chow A | display-authors = 6 | title = Population pharmacokinetic analysis of panitumumab in patients with advanced solid tumors | journal = Journal of Clinical Pharmacology | volume = 49 | issue = 10 | pages = 1142–56 | date = October 2009 | pmid = 19723673 | doi = 10.1177/0091270009344989 | s2cid = 25766549 }} 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|date=July 2022}}

Panitumumab was generated using Abgenix'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.{{Cite web | url= http://adisinsight.springer.com/drugs/800008663 | title= Panitumumab - Amgen | work= AdisInsight | access-date= 2017-01-27 | archive-date= 2017-11-03 | archive-url= https://web.archive.org/web/20171103072250/http://adisinsight.springer.com/drugs/800008663 | url-status= live }} Panitumumab is licensed to Dr. Reddy's Laboratories{{Cite web | url= https://www.drreddys.com/media/903958/press-release_amgen-deal-2016.pdf}} in India and GlaxoSmithKline in the UK.{{citation needed|date=July 2022}}

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.{{cite journal | vauthors = Gibson TB, Ranganathan A, Grothey A | title = Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer | journal = Clinical Colorectal Cancer | volume = 6 | issue = 1 | pages = 29–31 | date = May 2006 | pmid = 16796788 | doi = 10.3816/CCC.2006.n.01 }} In July 2009, the FDA updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab and cetuximab) indicated for the treatment of metastatic colorectal cancer to include information about KRAS mutations.{{cite web| url=https://www.genomeweb.com/dxpgx/fda-adds-kras-testing-info-vectibix-erbitux-labels| title=FDA updates Vectibix and Erbitux labels with KRAS testing info| date=20 July 2009| access-date=2 December 2014| archive-date=3 March 2016| archive-url=https://web.archive.org/web/20160303233107/https://www.genomeweb.com/dxpgx/fda-adds-kras-testing-info-vectibix-erbitux-labels| url-status=live}}{{MEDRS|date=December 2014}} This was the result of a study, which demonstrated lack of benefit with Panitumumab in patients who carried NRAS mutations.{{cite journal | vauthors = Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD | display-authors = 6 | title = Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer | journal = The New England Journal of Medicine | volume = 369 | issue = 11 | pages = 1023–34 | date = September 2013 | pmid = 24024839 | doi = 10.1056/NEJMoa1305275 | s2cid = 14556160 | doi-access = free }}

It is also approved as a first-line agent in combination with FOLFOX.{{Cite web | url=https://www.uptodate.com/contents/panitumumab-drug-information | title=UpToDate | access-date=2017-01-27 | archive-date=2017-02-02 | archive-url=https://web.archive.org/web/20170202074641/https://www.uptodate.com/contents/panitumumab-drug-information?source=search_result&search=panitumumab&selectedTitle=1~33 | url-status=live }}

Panitumumab is being studied in numerous phase II and III clinical trials. Phase III clinical trials include treatment of esophageal cancer,{{ClinicalTrialsGov|NCT01627379|Cisplatin and 5-FU +/- Panitumumab for Patients With Nonresectable, Advanced or Metastatic Esophageal Squamous Cell Cancer}} urothelial carcinoma,{{ClinicalTrialsGov| NCT00460265|I-MVAC +/- Panitumumab as First-line Treatment of Advanced Urothelial Carcinoma Without H-Ras Nor K-Ras Mutations}} metastatic head and neck cancer,{{ClinicalTrialsGov| NCT00460265|Study of Panitumumab Efficacy in Patients With Recurrent and/or Metastatic Head and Neck Cancer}} and liver metastasis in colorectal cancer.{{ClinicalTrialsGov|NCT02162563|Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases}} Early trials showed limited efficacy in patients with malignant melanoma, bladder cancer, prostate cancer, and renal cell carcinoma.

Although they both target the EGFR, panitumumab (IgG2) and cetuximab (IgG1) differ in their isotype and they might differ in their mechanism of action. Monoclonal antibodies of the IgG1 isotype may activate the complement pathway and mediate antibody-dependent cellular cytotoxicity (ADCC).[http://www.healthvalue.net/IgG1_IgG2.html HealthValue: IgG1 & IgG2] {{Webarchive|url=https://web.archive.org/web/20190605114213/http://www.healthvalue.net/IgG1_IgG2.html |date=2019-06-05 }}{{MEDRS|date=December 2014}} 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.{{cite journal | vauthors = Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Zhang K, Murugappan S, Sidhu R | display-authors = 6 | title = Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study | journal = The Lancet. Oncology | volume = 15 | issue = 6 | pages = 569–79 | date = May 2014 | pmid = 24739896 | doi = 10.1016/S1470-2045(14)70118-4 | hdl = 2381/43402 | url = https://figshare.com/articles/journal_contribution/10227896 | hdl-access = free }}

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• {{cite journal | vauthors = Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD | display-authors = 6 | title = Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer | journal = Journal of Clinical Oncology | volume = 26 | issue = 10 | pages = 1626–34 | date = April 2008 | pmid = 18316791 | doi = 10.1200/JCO.2007.14.7116 | url = https://air.unimi.it/bitstream/2434/349676/2/2008%20Amado%20et%20al%20J%20Clin%20Oncol.pdf | hdl = 2434/349676 | hdl-access = free | access-date = 2019-09-02 | archive-date = 2021-10-17 | archive-url = https://web.archive.org/web/20211017134751/https://air.unimi.it/retrieve/handle/2434/349676/509114/2008%20Amado%20et%20al%20J%20Clin%20Oncol.pdf | url-status = live }}
• {{cite journal | vauthors = Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG | display-authors = 6 | title = 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 = Journal of Clinical Oncology | volume = 25 | issue = 13 | pages = 1658–64 | date = May 2007 | pmid = 17470858 | doi = 10.1200/JCO.2006.08.1620 }}

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• {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/panitumumab | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Panitumumab }}

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