Trastuzumab*

Medical Policy: 05.01.24 
Original Effective Date: June 2009 
Reviewed: August 2011 
Revised: July 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: 

Trastuzumab, marketed as Herceptin®, is a humanized monoclonal antibody against the extracellular domain of the human epidermal growth factor receptor 2 (HER2) gene located on chromosome 17q. HER2 encodes a transmembrane ligand orphan receptor tyrosine kinase that amplifies the signal provided by other members of the HER family by forming heterodimers with them. HER2 activation and dimerization causes alterations in several complex downstream-signaling cascades that are involved in regulation of cell growth, proliferation, migration, adhesion, and survival, and thus has been implicated in oncogenesis. The HER2 gene is amplified and overexpressed in 20% to 30% of breast cancers as well as other epithelial cancers, including ovarian, thyroid, lung, salivary gland, stomach, colon, and prostate.

Trastuzumab has received U. S. Food and Drug Administration (FDA) marketing approval for treatment of HER2-positive breast cancer in both the adjuvant and metastatic settings. In October 2010, the FDA approved trastuzumab for the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

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Prior Approval: 

Prior approval is recommended.  Submit a prior approval/treatment request now. ( 1MB)

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Policy: 

Trastuzumab for the treatment of metastatic breast cancer may be considered medically necessary if all of the following criteria are met:

• The tumor(s) overexpress the HER2 protein as detected by an appropriate in-vitro immunohistochemical assay or fluorescence in situ hybridization (FISH) assays.
• The agent is being used as any one of the following:
  • Combination therapy with paclitaxel in individuals who have not received chemotherapy for metastatic disease
  • As a single agent in individuals who have received one or more chemotherapy agents for the metastatic disease

Trastuzumab for the treatment of breast cancer may be considered medically necessary in patients with HER2 overexpressing, node positive disease OR HER2 overexpressing high-risk node-negative disease if all of the following criteria are met:

• The tumor(s) overexpress the HER2 protein as detected by an appropriate in-vitro immunohistochemical assay or fluorescence in situ hybridization (FISH) assays.
• The agent is being used as any one of the following:
  • An adjuvant agent in combination with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel
  • An adjuvant agent with docetaxel and carboplatin
  • A single agent following multi-modality anthracycline-based therapy

Trastuzumab may be considered medically necessary for the preoperative treatment of breast cancer when all of the following criteria are met:

• The tumor(s) overexpress the HER2 protein as detected by an appropriate in-vitro immunohistochemical assay or fluorescence in situ hybridization (FISH) assays.
• The agent is being used in combination with paclitaxel followed in combination with fluorouracil, epirubicin and cyclophosphamide, in stage IIA, IIB, or T3, N1, M0 disease (ductal, lobular, mixed type, or metaplastic histologies) that is node-positive or node-negative and 1.0 cm or greater, in patients who desire breast preservation and fulfill criteria for breast-conserving surgery except for tumor size, OR for patients with locally advanced disease (stage IIIA, IIIB, or IIIC, including inflammatory breast cancer).

Trastuzumab may be considered medically necessary for the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

For the purposes of this medical policy, serum measurement of HER2 extracellular domain is considered investigational as a predictor of response to treatment

Appropriate cardiac assessment to evaluate left ventricular function is recommended in all patients prior to and during treatment with trastuzumab.

All other uses of trastuzumab not described above are considered investigational.

Targeted therapy using trastuzumab against human epidermal growth factor receptor type-2 (HER2) has shown survival benefit for primary and metastatic breast cancer and has become the accepted and usual therapy for patients with HER2-positive breast cancer.

One phase III trial has reported outcomes with the use of trastuzumab in advanced gastric or gastroesophageal cancer, with a 2 month overall survival benefit in the trastuzumab arm and no difference in severe adverse events between the group that received chemotherapy plus trastuzumab versus chemotherapy alone.

Studies examining the possible uses of trastuzumab in HER2-positive cancers other than breast and gastric/gastroesophageal cancers have consisted mainly of small uncontrolled series. For the most part, results have been disappointing, with little to no improvement in outcomes; studies have also suffered from the low percentage of HER2 overexpression in certain tumors.

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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.
• J9355 Trastuzumab 10 mg

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Selected References: 

• Seidman AD, Berry D, Cirrincione C et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008; 26:1642-1649.
• Smith I, Proctor M, Gelber RD et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6 369(9555):29-36.
• Burstein HJ, Keshaviah A, Baron AD et al. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1; 110(5): 965-972.
• Buzdar AU, Ibrahim NK, Francis D et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 2005 Jun; 23(16):3676-3685.
• Untch M, Gelber RD, Jackisch C et al. Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol. 2008 Jun; 19(6):1090-6.
• National Comprehensive Cancer Network (NCCN). Breast Cancer. Practice Guidelines in Oncology – v.1.2009.
• Liberato NL, Marchetti M, Barosi G. Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer.  J Clin Oncol 2007 Feb 20; (25)6: 625-33.
• Piccart-Gebhart MJ, Proctor M, Leyland-Jones B et al; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659-1672.
• Swanton C, Futreal A, Eisen T. HER2-targeted therapies in non-small cell lung cancer. Clin Cancer Res. 2006; 12(14 Pt 2):4377s-4383s.
• Lennon S, Barton C, Banken L et al. Utility of serum HER2 extracellular domain assessment in clinical decision making: pooled analysis of four trials of trastuzumab in metastatic breast cancer. J Clin Oncol 2009 Apr; 27(10):1685-93.
• Leary AF, Hanna WM, van de Vijver M et al. Value and limitations of measuring HER-2 extracellular domain in the serum of breast cancer patients. J Clin Oncol 2009 Apr; 27(10):1694-1705.
• Van Cutsem E, Kang Y, Chung H et al. Efficacy results from the ToGA trial: A phse III study of trastuzumab added to standard chemotherapy (CT) in first-line epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). J Clin Oncol. 2009;27:18s (suppl; abstr LBA4509).
• Okines AF, Cunningham D. Trastuzumab in gastric cancer. Eur J Cancer. 2010 Jul;46(11):1949-59. Epub 2010 Jun 11.
• Javle M, Hsueh CT. Recent advances in gastrointestinal oncology—updates and insights from the 2009 annual meeting of the American Society of Clinical Onocology. J Hematol Oncol. 2010 Mar 23; 3:11.
• Wagner AD, Unversagt S, Grothe W et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010 Mar 17; 3:CD004064.
• Roukos DH. Targeting gastric cancer with trastuzumab: new clinical practice and innovative developments to overcome resistance. Ann Surg Oncol. 2010 Jan; 17(1): 14-7. Epub 2009 Oct 20.
• Kaufman B, Mackey JR, Clemens MR et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37.
• Bang YJ, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet. 2010 Aug 28;376(9742):687-97.

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Policy History: 

Date                                        Reason                               Action

August 2011                           Annual review                     Policy renewed

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*Current Procedural Terminology © 2010 American Medical Association. All Rights Reserved.