Panitumumab (Vectibix^TM)*

Medical Policy: 05.01.15 
Original Effective Date: November 2006 
Reviewed: April 2012 
Revised: March 2010 

Benefit Application
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

Description: 

Panitumumab, marketed under the trade name Vectibix™, is a fully-human monoclonal antibody against the human epidermal growth factor receptor (EGFR), which is over-expressed in many cancers, including colorectal. Clinical studies have shown that panitumumab has significant single-agent activity and improves progression-free survival when compared with best supportive care.

The RAS-RAF-MAP kinase pathway is activated in the EGFR cascade. RAS proteins are G-proteins that cycle between active (RAS-GTP) and inactive (RAS-GDP) forms, in response to stimulation from a cell surface receptor such as EGFR, and act as a binary switch between the cell surface EGFR and downstream signaling pathways. The KRAS gene can harbor oncogenic mutations that result in a constitutively activated protein, independent of EGFR ligand binding, rendering antibodies to the upstream EGFR ineffective. KRAS mutations are found in approximately 30-50% of colorectal cancer tumors and are common in other tumor types.

Data from randomized controlled trials have consistently shown a lack of clinical response to panitumumab and cetuximab in patients with mutated KRAS, with tumor response and prolongation of progression-free survival observed only in patients with wild-type KRAS mutations. Several single-arm studies that have retrospectively analyzed KRAS mutation status and tumor response rate in patients with metastatic colorectal cancer (mCRC) have shown a consistent lack of response to panitumumab or cetuximab in patients with KRAS mutation. Some of these studies have also demonstrated progression-free and overall survival benefit when the use of EGFR inhibitors is limited to patients with wild-type KRAS.

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Prior Approval: 

Prior approval is recommended for panitumumab. Submit a prior approval/treatment request now. ( 74KB)

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Policy: 

Panitumumab may be considered medically necessary when both the following criteria are met:

• Treatment of EGFR-expressing, metastatic colorectal cancer with disease  progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens: AND
• KRAS mutation analysis has demostrated the tumor expresses the wild-type KRAS gene.

NOTE: KRAS mutation analysis is required prior to treatment of EGFR-expressing metastatic colorectal cancer with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotescan-containing chemotherapy regimens. Please see medical policy 02.04.20; KRAS Mutation Analysis in Metastatic Colorectal Cancer.

The use of panitumumab in persons who have experienced clinical failure on cetuximab is considered investigational.

All other uses of panitumumab are considere investigational.

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Procedure Codes and Billing Guidelines: 

• To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD-9-CM diagnostic codes.
• J9303 Injection Panitumumab, 10 mg 

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Selected References: 

• Saif MW, Cohenuram M. Role of panitumumab in the management of metastatic colorectal cancer. Clin Colorectal Cancer. 2006 Jul;692):118-24.
• Gibson TB, Ranganathan A, Grothey A. Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clin Colorectal Cancer 2006 May;6(1):13.
• Wainberg Z, Hecht JR. Panitumumab in colon cancer: a review and summary of ongoing trials. Expert Opin Biol Ther. 2006 Nov;6(11):1229-35.
• Siena S, Peeters M, Van Cutsem E et al. Association of progression-free survival with patient-reported outcomes and survival: results from a randomised phase 3 trial of panitumumab. Br J cancer. 2007 Dec 3;97(11):1469-74. Epub 2007 Nov 27.
• Hecht JR, Patnaik A, Berlin J et al. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer. 2007 Sep 1;110(5):980-8.
• Socinski MA. Antibodies to the epidermal growth factor receptor in non small cell lung cancer: current status of matuzumab and panitumumab. Clin Cancer Res. 2007 Aug 1;13(15 pt 2):s4597-601.
• Lopez-Albaitero A, Ferris RL. Immune activation by epidermal growth factor receptor-specific monoclonal antibody therapy for head and neck cancer. Ach Otolarngol Head Neck Surg. 2007 Dec;133(12):1277-81.
• Peeters M, Balfour J, Arnold D. Review Article: Panitumumab- A Fully Human Anti-EGFR Monoclonal Antibody for Treatment of Metastatic Colorectal Cancer. Aliment Pharmacol Ther. 2008;28(3):269-81.
• Amado RG, Wolf M, Peeters M et al. Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2008 Apr 1; 26(10):1626-34.
• Hecht JR, Mitchell E, Chidiac T et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol. 2009; 27(5): 672-680.
• Freeman DJ, Juan T, Reiner M et al. Associaton of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone. Clin Colorectal Cancer. 2008; 7(3): 184-90.
• Bardelli A, Siena S. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 2010 Jan 25. Epub ahead of print as 10.1200/JCO.2009.24.6116.
• Douillard J-Y, Siena S, Cassidy J et al. Randomized, phase III trial of panitumumab with Infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX 4) versus FOLFOX 4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol 2010 Nov 1; 28(31): 4697-4705. doi: 10.1200/JCO.2009.27.4860.
• Peeters M, Price TJ, Cervantes A et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 2010 Nov 1; 28(31):4706-13. doi:10.1200/JCO.2009.27.6055.
• Cripps C, Gill S, Ahmed S et al. Consensus recommendations for the use of anti-EGFR therapies in metastatic colorectal cancer. Curr Oncol. 2010 Nov; 17(6):39-45.
• Odom D, Barber B, Bennett L et al. Health-related quality of life and colorectal cancer-specific symptoms in patients with chemotherapy-refractory metastatic disease treated with panitumumab. Int J Colorectal Dis 2011; 26:173-81. doi:10.1007/s00384-010-1112-5.
• Wasif-Saif M, Kaley K, Chu E et al. Safety and Efficacy of panitumumab therapy after progression with cetuximab: experience at two institutions. Clin Colorectal Cancer 2010 Dec;9(5):315-18. doi:10.3816/CCC.2010.n.046.
• Douillard JY, Siena S, Cassidy J et al. Randomized, Phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol Nov 1 2010; 28(31):4697-4705.
• Peeters M, Price TJ, Cervantes A et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol Nov 1 2010; 28(31):4706-13.  

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Policy History: 

Date                                        Reason                               Action

April 2011                              Annual review                     Policy renewed

April 2012                              Annual review                     Policy renewed

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Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.