Panitumumab
Panitumumab is a recombinant human IgG2 kappa monoclonal antibody which binds specifically to the human epidermal growth factor receptor (EGFR). EGFR is expressed in multiple cell lines including epithelial tissues and is over-expressed in certain cancers. EGFR functions in a complex cascade system that affects gene transcription involved with cellular growth, motility and proliferation. By binding to EGFR, panitumumab interrupts the cascade which ultimately leads to the development of cancer. This results in inhibition of excessive cell growth, induction of apoptosis, and decreased proinflammatory cytokine and vascular growth factor production.
In the EGFR cascade, certain proteins including the KRAS protein normally function as switches in the kinase pathway activated between cell surface EGFR and downstream signaling. The gene mapping normal, non-mutated KRAS production is referred to as a wild-type gene. Mutations in this KRAS gene occur in 30% to 50% of colorectal cancers as well as other tumor types. These mutations in KRAS cause activation of the EGFR pathway beyond the point at which panitumumab would bind with EGFR and interrupt the cascade. This renders panitumumab and other anti-EGFR agents ineffective against those tumors expressing KRAS mutations.
Another common mutation is found in the BRAF gene, a serine/threonine kinase. BRAF encodes a component downstream of the RAS proteins in the EGFR cascade. The BRAF gene is important for transducing mitogenic signals from the cell surface. BRAF mutations have been found in thyroid, colorectal and lung cancers as well as in a majority of malignant melanomas, however specific targeting and treatment of BRAF-dependent tumors remains under investigation.
An example of a preparation of panitumumab is Vectibix®.
Panitumumab for the treatment of colorectal carcinoma is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Panitumumab for the treatment of other conditions/diseases, including, but not limited to, the following: metastatic renal cell carcinoma and advanced non-small cell lung cancer is considered investigational. (See Applicable Tennessee State Mandate Requirements below.)
Testing for mutation of the BRAF gene in the use of panitumumab is considered investigational.
MEDICAL APPROPRIATENESS
Panitumumab for the treatment of colorectal carcinoma is considered medically appropriate if ALL of the following criteria are met:
Disease is metastatic (mCRC)
KRAS gene is normal (e.g., without mutation, wild type)
Disease is progressing on or after ANY ONE of the following chemotherapy regimens:
Fluoropyrimidine-containing
Oxaliplatin-containing
Irinotecan-containing
Treatment is to be as a single agent
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
The NCCN Drugs & Biologics Compendium recognizes additional uses for panitumumab beyond the FDA-approved labeling in the treatment of the following conditions (Refer to the NCCN Drugs & Biologics Compendium or NCCN Clinical Practice Guidelines for detailed recommendations):
Colon cancer
Rectal cancer
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
In a search through the published literature, no controlled studies were found that validate the use of panitumumab in the treatment/prevention of any other conditions/diseases.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (11:2010). KRAS and BRAF Mutation Analysis in Metastatic Colorectal Cancer. (2.04.53). Retrieved January 6, 2011 from BlueWeb.
Lexi-Comp Online. (20109). AHFS DI. Panitumumab. Retrieved August 12, 2010 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2010). Panitumumab. Retrieved August 12, 2010 from MICROMEDEX Healthcare Series.
National Comprehensive Cancer Network. (2010). NCCN Drugs & Biologics Compendium™. Panitumumab. Retrieved August 12, 2010 from the National Comprehensive Cancer Network.
U. S. Food and Drug Administration. (2009, July). Vectibix® (panitumumab) label. Retrieved August 12, 2010 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125147s080lbl.pdf.
ORIGINAL EFFECTIVE DATE: 6/9/2007
MOST RECENT REVIEW DATE: 2/23/2011
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
Pharmaceutical Decision Support Tree
Panitumumab (Vectibix®)
Is there a request for BRAF mutation testing?
If yes, this does not meet medical necessity and/or medical appropriateness criteria
If no, go to question #2
Is the requested medication being used to treat metastatic renal cell carcinoma or advanced non-small cell lung cancer?
If yes, this does not meet medical necessity and/or medical appropriateness criteria
If no, go to question #3
Does the individual have a diagnosis of colorectal carcinoma?
If yes, go to question #4
If no, this does not meet medical necessity and/or medical appropriateness criteria
Does the individual show evidence of ALL of the following?
Disease is metastatic (mCRC)
KRAS gene is normal (e.g., without mutation, wild type)
Disease is progressing on or after ANY ONE of the following chemotherapy regimens:
Fluoropyrimidine-containing chemo
Oxaliplatin-containing chemo
Irinotecan-containing chemo
Treatment is to be as a single agent
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.