Drug/Small Molecule:
panitumumab

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB annotates drug labels containing pharmacogenetic information approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency, Japan (PMDA). PharmGKB annotations provide a brief summary of the PGx in the label, an excerpt from the label and a downloadable highlighted label PDF file. A list of genes and phenotypes found within the label is mapped to label section headers and listed at the end of each annotation. PharmGKB also attempts to interpret the level of action implied in each label with the "PGx Level" tag.

Sources:

  • FDA Information is gathered from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" and from FDA-approved labels brought to our attention. Please note that drugs may be removed from or added to the FDA's Table without our knowledge. We periodically check the Table for changes and update PharmGKB accordingly. Drugs listed on the Table to our knowledge are tagged with the Biomarker icon. A drug label that has been removed from the Table will not have the Biomarker icon but will continue to have an annotation on PharmGKB stating the label has been removed from the FDA's Table. We acquire label PDF files from DailyMed.
  • EMA European Public Assessment Reports (EPARs) that contain PGx information were identified from [Article:24433361] and also by searching for drugs for which we have PGx-containing FDA drug labels.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA, PMDA or other Medicine Agencies around the world - please contact feedback.



last updated 10/25/2013

FDA Label for panitumumab and EGFR, KRAS

Genetic testing required

Summary

The panitumumab drug label contains information about EGFR-expressing metastatic colorectal carcinoma with disease progression on or following certain chemotherapy regimens. Detection of EGFR protein expression is necessary for selection of patients appropriate for Vectibix therapy. The label was updated to include information about treatment of patients with KRAS mutations. Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for Vectibix in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Vectibix is not recommended for the treatment of colorectal cancer with these mutations.

There's more of this label. Read more.


last updated 10/27/2013

European Medicines Agency (EMA) Label for panitumumab and KRAS

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) for panitumumab (Vectibix) contains information regarding the requirement for testing of KRAS mutations before initiating treatment, as the drug is indicated for patients with wildtype KRAS.

There's more of this label. Read more.



PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
therascreen KRAS RGQ PCR Kit KRAS KRAS:Gly12Asp , KRAS KRAS:Gly12Ala , KRAS KRAS:Gly12Val , KRAS KRAS:Gly12Ser , KRAS KRAS:Gly12Arg , KRAS KRAS:Gly12Cys , KRAS KRAS:Gly13Asp
KRAS Mutation Detection Kit - Mutector II KRAS KRAS:Gly12Asp , KRAS KRAS:Gly12Ala , KRAS KRAS:Gly12Val , KRAS KRAS:Gly12Ser , KRAS KRAS:Gly12Arg , KRAS KRAS:Gly12Cys , KRAS KRAS:Gly13Asp , KRAS KRAS:Gly13Ser , KRAS KRAS:Gly13Arg , KRAS KRAS:Gly13Cys , KRAS KRAS:Gly13Ala , KRAS KRAS:Gly13Val

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all panitumumab variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs10034692 15630454A>G, 37578A>G, 75419787A>G
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs1017733 *1825C>T, 15463017C>T, 75252350C>T
C > T
3' UTR
No VIP available No Clinical Annotations available VA
rs11568972 110889007A>C, 1450-1120A>C, 1576-1120A>C, 35436728A>C, 59968A>C
A > C
Intronic
No VIP available No Clinical Annotations available VA
rs11568993 110897315C>T, 1851C>T, 1977C>T, 35445036C>T, 68276C>T, Cys617=, Cys659=
C > T
Synonymous
Cys659Cys
No VIP available No Clinical Annotations available VA
rs11725706 15538775G>A, 75328108G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs11942466 15632745C>A, 39869C>A, 75422078C>A
C > A
Not Available
No VIP available No Clinical Annotations available VA
rs13104811 13103G>A, 15605979G>A, 75395312G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs1353295 15539789G>A, 75329122G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs2074390 110910016G>A, 2608+151G>A, 2734+151G>A, 35457737G>A, 80977G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs2132065 15535971A>T, 75325304A>T
A > T
Not Available
No VIP available No Clinical Annotations available VA
rs2227983 147531G>A, 147531G>C, 147531G>T, 1562G>A, 1562G>C, 1562G>T, 4818624G>A, 4818624G>C, 4818624G>T, 55229255G>A, 55229255G>C, 55229255G>T, Arg521Lys, Arg521Met, Arg521Thr, EGFR: 497G/A, EGFR:1562G>A, EGFR:R497K, R497K, R521K
G > A
G > T
G > C
Missense
Arg521Thr
Arg521Lys
Arg521Met
No VIP available No Clinical Annotations available VA
rs3913032 15547526A>C, 75336859A>C
A > C
Not Available
No VIP available No Clinical Annotations available VA
rs4444903 -382A>G, 110834110A>G, 35381831A>G, 5071A>G
A > G
5' UTR
No VIP available No Clinical Annotations available VA
rs4698803 110914427A>T, 2633A>T, 2735-1462A>T, 2759A>T, 35462148A>T, 85388A>T, Glu878Val, Glu920Val
A > T
Missense
Glu920Val
No VIP available CA VA
rs61764370 *2505T>G, *2626T>G, 18120348A>C, 25360224A>C, 48631T>G
A > C
3' UTR
No VIP available No Clinical Annotations available VA
rs6447003 15597581G>C, 4705G>C, 75386914G>C
G > C
Not Available
No VIP available No Clinical Annotations available VA
rs6533485 110927563G>C, 3166-1745G>C, 3169-1745G>C, 3292-1745G>C, 35475284G>C, 98524G>C
G > C
Intronic
No VIP available No Clinical Annotations available VA
rs6850557 110911015G>A, 2608+1150G>A, 2734+1150G>A, 35458736G>A, 81976G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs712829 -216G>T, 216G>T, 4676124G>T, 5031G>T, 55086755G>T, EGFR:-216G>T
G > T
5' UTR
No VIP available No Clinical Annotations available VA
rs7687621 15460493T>C, 429-618T>C, 75249826T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs929446 110883344C>T, 1186+203C>T, 1312+203C>T, 35431065C>T, 54305C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs9996584 15632628A>G, 39752A>G, 75421961A>G
A > G
Not Available
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142

Overview

Generic Names
  • ABX-EGF
  • panitumumab
Trade Names
  • Vectibix
  • Vectibix (Amgen)
Brand Mixture Names

PharmGKB Accession Id:
PA162373091

Description

Panitumumab (ABX-EGF) is a recombinant human IgG2 monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). This drug is an antineoplastic agent.

Source: Drug Bank

Indication

For the treatment of EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR.

Source: Drug Bank

Pharmacology

Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human Epidermal Growth Factor Receptor (EGFR). EGFR is a transmembrane glycoprotein that belongs to the subfamily of type I receptor tyrosine kinases. Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, including those of the colon and rectum. Interaction of EGFR with its normal ligands causes phosphorylation and activation of a series of intracellular proteins that will in turn regulate the transcription of genes involved with cellular growth and survival, motility, and prolieration. Signal transduction through EGFR leads to the activation of the wild type KRAS gene, but the presence of an activating somatic mutation of the KRAS gene within a cancer cell can result in the dysregulation of signaling pathways and resistance to EGFR inhibitor therapy.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Half-Life

7.5 days (range: 4-11 days)

Source: Drug Bank

Toxicity

Panitumumab was shown to cause skin, ocular and mucosal related toxicities in 90% of patients receiving panitumumab. Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage, were reported.

Source: Drug Bank

Clearance

Chemical Properties

Canonical SMILES

Not Available

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. EGFR Inhibitor Pathway, Pharmacodynamics
    Model non-tissue specific cancer cell displaying genes that may be involved in the treatment using epidermal growth factor receptor specific tyrosine kinase inhibitors or monoclonal antibodies.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
AREG
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
EGF
EGFR
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
EREG
No Dosing Guideline available DL CA VA No VIP available No VIP available
KRAS

Drug Targets

Gene Description
EGFR (source: Drug Bank)
No related drugs are available.

Curated Information ?

Publications related to panitumumab: 17

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Emerging landscape of oncogenic signatures across human cancers. Nature genetics. 2013. Ciriello Giovanni, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for the epidermal growth factor receptor. Pharmacogenetics and genomics. 2013. Hodoglugil Ugur, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Intergenic polymorphisms in the amphiregulin gene region as biomarkers in metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan. The pharmacogenomics journal. 2013. Sebio A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The LCS6 polymorphism in the binding site of let-7 microRNA to the KRAS 3'-untranslated region: its role in the efficacy of anti-EGFR-based therapy in metastatic colorectal cancer patients. Pharmacogenetics and genomics. 2013. Sebio Ana, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy. Pharmacogenomics. 2013. Weng Liming, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A Novel Fully Automated Molecular Diagnostic System (AMDS) for Colorectal Cancer Mutation Detection. PloS one. 2013. Kitano Shiro, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy. The pharmacogenomics journal. 2012. Savonarola A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity. The pharmacogenomics journal. 2011. Parmar S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Prospective-retrospective biomarker analysis for regulatory consideration: white paper from the industry pharmacogenomics working group. Pharmacogenomics. 2011. Patterson Scott D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetic tests in cancer chemotherapy: what physicians should know for clinical application. The Journal of pathology. 2011. Lee Soo-Youn, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomic contribution to drug response. Cancer journal (Sudbury, Mass.). 2011. Watson Roshawn G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The increasing role of pharmacogenetics in the treatment of gastrointestinal cancers. Gastrointestinal cancer research : GCR. 2009. Yalçin Suayib. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and biomarkers in colorectal cancer. The pharmacogenomics journal. 2009. Strimpakos A S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of EGFR and VEGF inhibition. Drug discovery today. 2007. Pander Jan, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
UniProtKB:
P01859
National Drug Code Directory:
55513-954-01
DrugBank:
DB01269
Therapeutic Targets Database:
DNC000135
FDA Drug Label at DailyMed:
e0fa4bca-f245-4d92-ae29-b0c630a315c2

Clinical Trials

These are trials that mention panitumumab and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.