L28849-LCD

Automated World Health

Local Coverage Determination (LCD) for Gene Expression Profiling Panel for

use in the Management of Breast Cancer Treatment (L28849)

Contractor Information

Contractor Name

First Coast Service Options, Inc.

Contractor Number

09101

Contractor Type

MAC - Part A

LCD Information

Document Information

LCD ID Number L28849

LCD Title

Gene Expression Profiling Panel for use in the Management of Breast Cancer Treatment

Contractor's Determination Number A84999

Primary Geographic Jurisdiction Florida

Oversight Region Region IV

AMA CPT/ADA CDT Copyright Statement

Applicable FARS/DFARS Apply to Government Use. Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein. The Code on Dental Procedures and Nomenclature (Code) is published in Current Dental Terminology (CDT). Copyright © American Dental Association. All rights reserved. CDT and CDT-2010 are trademarks of the American Dental Association.

Original Determination Effective Date

For services performed on or after 02/16/2009 Original Determination Ending Date

Revision Effective Date

For services performed on or after 04/10/2012 Revision Ending Date

CMS National Coverage Policy 42 CFR 410.32

42 CFR 410.42

42 CFR 414.510

42 CFR 414.50

CMS Change Request 5573, dated 08/17/2007

CMS Manual System, Pub 100-02, Medicare Benefit Policy Manual, Chapter 6, Section 20 CMS Manual System, Pub 100-02, Medicare Benefit Policy Manual, Chapter 15, Section 80.1

CMS Manual System, Pub 100-04, Medicare Claims Processing Manual, Chapter 1, Section 10.1.

CMS Manual System, Pub 100-04, Medicare Claims Processing Manual, Chapter 16, Sections 40.8 and 120.1

CMS Manual System, Pub 100-08, Medicare Program Integrity Manual, Chapter 3, Section 3.4.1.2

Indications and Limitations of Coverage and/or Medical Necessity

Genomics focuses on how the complex set of genes in the genome are expressed and interact to regulate cell behavior in health and disease. An important genomic parameter is the pattern of gene expression, which can be ascertained by measuring the levels of expressed ribonucleic acid (RNA). To date, therapeutic decisions for locally advanced breast cancer are mainly guided by clinicopathological parameters, such as patient age and functional status, comorbidities, estrogen receptor status, tumor grade, tumor size and lymph node status. Clinical studies have shown that incorporation of gene expression signatures into clinical risk stratification may be useful for prognostic and therapeutic strategies in breast carcinoma.

The application of gene expression profiling using Oncotype DX TM is employed to identify patients who are predicted to obtain the most therapeutic benefit from adjuvant tamoxifen and may not require adjuvant chemotherapy. The Oncotype DX TM (Genomic Health, Redwood City, California), uses reverse transcription polymerase chain reaction (RT-PCR) to determine the expression of a panel of 21 genes isolated from formalin- fixed, paraffin-embedded tissue (FPET).

A Recurrence Score TM (RS) is calculated from the gene expression results using a proprietary Oncotype DX TM algorithm, which is then used to assign a patient to one of three groups by estimated risk of distant recurrence: low, intermediate and high. Patients with high recurrence scores (RS) appear to achieve relatively more benefit from adjuvant chemotherapy.

This test is provided throughout the United States by the Clinical Laboratory Improvement Amendments (CLIA)- regulated laboratory of Genomic Health, Inc. in Northern California. Therefore, when this test is a Part B service, most or all coverage decisions for Medicare beneficiaries are made by the Part B contractor serving Genomic Health, Inc., which is National Heritage Insurance Company (NHIC).

INDICATIONS

First Coast Service Options, Inc. (FCSO) will consider the application of gene expression profiling using Oncotype DX TM as medically reasonable and necessary, with case by case review as needed, when used to assess the need for adjuvant chemotherapy in patients with recently diagnosed breast cancer (six months or less have elapsed) when all of the following criteria are met:

• Breast cancer is nonmetastatic (node-negative) (lymph nodes with micrometastases are not considered positive); and

• Estrogen positive breast carcinoma with 1-3 positive nodes; and

• Breast cancer is unilateral and non-fixed (i.e., tumor not adhered to chest wall); and

• Breast tumor is hormone receptor-positive (estrogen receptor (ER)-positive or progesterone receptor (PR)- positive); and

• Breast tumor is HER2-receptor negative; and

• Breast tumor size is 0.6-1 cm with moderate/poor differentiation or unfavorable features (e.g., angiolymphatic invasion, high nuclear grade, or high histologic grade), OR tumor size is >1 cm; and

• Breast tumor is stage 1 or stage II; and

• Breast cancer will be treated with hormonal therapy; and

• Adjuvant chemotherapy is not precluded due to any other factor (e.g., advanced age and/or significant co- morbidities); and

• Testing is being done specifically to guide the decision as to whether or not adjuvant chemotherapy will be used and, prior to testing the patient and oncologist have discussed the potential results of the test and agree to use the results to guide therapy (i.e., the patient will forgo adjuvant chemotherapy if Oncotype DX TM score is low).

Medical tests are covered only when ordered by the treating oncologist, when necessary for diagnosis or treatment decisions, and when used in patient care (42 CFR 410.32).

LIMITATIONS

All other uses of Oncotype DX TM are considered experimental or investigational; specifically, the following indications:

• To predict response to specific chemotherapy regimens

• Repeat Oncotype DX TM testing or testing of multiple tumor sites in the same patient

In a clinical trial, this test would typically be used for data collection and would not be considered a routine cost and, therefore, this service would not be billed.

Gene expression profiling as a technique of managing the treatment of breast cancer is considered investigational and not medically necessary when a gene profiling test other than the Oncotype DX TM breast cancer assay is used, including but not limited to:

• Breast Cancer Gene Expression Ratio

• MammaPrint®

• Rotterdam 76-Gene Signature

• The 41-gene signature assay

• Amsterdam 70-Gene Profile

Genomic Health public documents filed with the United States Securities and Exchange Commission (SEC) note that Oncotype DX TM is not currently regulated by the Food and Drug Administration (FDA) (neither approved nor disapproved), but this status could be subject to change. Determinations of the FDA, which directly affect the legality of marketing status would override this Local Coverage Determination (LCD).

Coding Information

Bill Type Codes:

Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims.

012x Hospital Inpatient (Medicare Part B only) 013x Hospital Outpatient

014x Hospital - Laboratory Services Provided to Non-patients 085x Critical Access Hospital

Revenue Codes:

Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory; unless specified in the policy services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes.

0301 Laboratory - Chemistry

CPT/HCPCS Codes

84999 UNLISTED CHEMISTRY PROCEDURE

ICD-9 Codes that Support Medical Necessity

174.0 - 174.9 MALIGNANT NEOPLASM OF NIPPLE AND AREOLA OF FEMALE BREAST - MALIGNANT NEOPLASM OF BREAST (FEMALE) UNSPECIFIED SITE

175.0 - 175.9 MALIGNANT NEOPLASM OF NIPPLE AND AREOLA OF MALE BREAST - MALIGNANT NEOPLASM OF OTHER AND UNSPECIFIED SITES OF MALE BREAST

V86.0* ESTROGEN RECEPTOR POSITIVE STATUS [ER+]

* ICD-9 code V86.0 is a secondary diagnosis code and should not be billed as the primary diagnosis; therefore, this diagnosis code (V86.0) must be billed with another diagnosis code from the list above.

Diagnoses that Support Medical Necessity N/A

ICD-9 Codes that DO NOT Support Medical Necessity XX000 Not Applicable

ICD-9 Codes that DO NOT Support Medical Necessity Asterisk Explanation

Diagnoses that DO NOT Support Medical Necessity N/A

General Information

Documentations Requirements

The following documentation should be available for review upon request:

• Patient history and physical; and

• Pathology report; and

• Documentation which indicates all of the following:

A. The results of the Oncotype DX TM test are expected to play a significant role in management of the patient; and

B. The patient is a candidate for possible adjuvant chemotherapy (i.e., chemotherapy is not precluded due to other factors) and testing is being done specifically to guide the decision as to whether or not adjuvant chemotherapy will be used; and

C. The genomic information derived from this test has been integrated with copathological parameters, such as patient age and functional status, comorbidities and tumor grade.

Oncotype DX TM should only be ordered after surgery and subsequent pathological examination of the tumor have been completed. The test should be ordered in the context of a physician-patient discussion regarding risk preferences and when the test result will aid the patient in making decisions regarding chemotherapy.

Providers should not submit additional information with the claim. FCSO may request it separately with an additional documentation request (ADR) letter.

Appendices

Utilization Guidelines It is expected that these services would be performed as indicated by current medical literature and/or standards of practice. When services are performed in excess of established parameters, they

may be subject to review for medical necessity.

Sources of Information and Basis for Decision

Acharya, C., Hsu, D., Anders, C., Anguiano, A., Salter, K., Walters, K., Redman, R., Tuchman, S., Moylan, C., Mukherjee, S., Barry, W., Dressman, H., Ginsburg, G., Marcom, K., Garman, K., Lyman, G., Nevins, J., & Potti, A.. (2008). Gene expression signatures, clinicopathological features, and individualized therapy in breast cancer. JAMA, 299(13), 1574-1587.

BlueCross and BlueShield Association Technology Evaluation Center (TEC) Assessment. (2005). Gene expression profiling for managing breast cancer treatment, 20(5). Retrieved March 25, 2008, from www.bcbs.com/tec.

Burstein, H., Paik, S., Ravdin, P., & Albain, K. (2006). Aduvant chemotherapy for patients with estrogen receptor- positive breast cancer. American Society of Clinical Oncology, 06, 49-55.

Cobleigh, M., Tabesh, B., Bitterman, P., Baker, J., Cronin, M., Liu, M., Borchik, R., Mosquera, J., Walker, M., & Shak, S. (2005). Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes. Clin Cancer Res, 11(24), 8623-8631.

Gianni, L., Zambetti, M., Clark, K., Baker, J., Cronin, M., Wu, J., Mariani, G., Rodriguez, J., Carcangiu, M., Watson, D., Valagussa, P., Rouzier, R, Symmans, F., Ross, J., Hortobagyi, G., Pusztai, L., & Shak, S. (2005). Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol, 23(29), 7265-7277.

Habel, L., Shak, S., Jacobs, M., Capra, A., Alexander, C., Pho, M., Baker, J., Walker, M., Watson, D., Hackett, J., Blick, N., Greenberg, D., Fehrenbacher, L., Langholz, B., & Quesenberry, C. (2006). A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Research, 8(R25) Retrieved April 1, 2008, online at: http://breast-cancer-research.com/content/8/3/R25.

Harris, L., Fritsche, H., Mennel, R., Norton, L., Ravdin, P., Taube, S., Somerfield, M., Hayes, D., & Bast, R. (2007). American society of clinical oncology 2007 update of recommendations for the use of tumor markers in breast cancer [ASCO Special Article]. Journal of Clinical Oncology, 25(33), 1-26.

Hornberger, J., Cosler, L., & Lyman, G. (2005). Economic analysis of targeting chemotherapy using a 21-gene RT

-PCR assay in lymph-node-negative, estrogen-receptor-positive, early-stage-breast cancer. The American Journal of Managed Care, 11(5), 313-324.

Huang, C., & Bredel, M. (2008). Use of gene signatures to improve risk estimation in cancer. JAMA, 299(13), 1605-1606.

Lyman, G., Cosler, L., Kuderer, N., & Hornberger, J. (2007). Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer. Cancer, 109(6), 1011-1018.

Marchionni, L., Wilson, R., Wolff, A., Marinopoulos, S., Parmigiani, G., Bass, E., & Goodman, S. (2008). Systematic review: Gene expression profiling assays in early-stage breast cancer. Annals of Internal Medicine, 148, 358-369.

Marchionni, L, Wilson, R., Marinopoulos, S., Wolff ,A., Parmigiani, G., Bass, E., & Goodman, S. (2008). Impact of gene expression profiling tests on breast cancer outcomes. Evidence

Report/Technology Assessment, (160). [Prepared by The Johns Hopkins University Evidence based Practice Center under contract No. 290-02-0018). AHRQ Publication No. 08-E002.

Rockville, MD: Agency for Healthcare Research and Quality. Retrieved March 25, 2008, from www.ahrq.gov.

Newman, L., & Singletary, S. (2007). Overview of adjuvant systemic therapy in early stage breast cancer. Surgical Clinics of North America, 87(2). Retrieved March 24, 2008, from www.mdconsult.com (90879021).

Paik, S., Tang, G., Shak, S., Kim, C., Baker, J., Kim, W., Cronin, M., Baehner, F., Watson, D., Bryant, J., Costantino, J., Geyer, C., Wickerham, D., & Wolmark, N. (2006). Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol, 24(23), 3726-3734.

Paik, S., Shak, S., Tang, G., Kim, C., Baker, J., Cronin, M., Baehner, F., Walker, M., Watson, D., Park, T., Hiller, W., Fisher, E., Wickerham, L., Bryant, J., & Wolmark, N. (2004). A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. The New England Journal of Medicine, 351(27), 2817-2826.

Advisory Committee Meeting Notes This Local Coverage Determination (LCD) does not reflect the sole opinion of the contractor or Contractor Medical Director. Although the final decision rests with the contractor, this LCD was

developed in cooperation with advisory groups, which includes representatives from numerous societies.

Start Date of Comment Period

End Date of Comment Period

Start Date of Notice Period 12/04/2008

Revision History Number 1

Revision History Explanation Revision Number: 1 Start Date of Comment Period: N/A

Start Date of Notice Period: 05/01/2012 Revised Effective Date: 04/10/2012

LCR A2012-039

April 2012 Connection

Explanation of Revision: LCD revised under the “Indications and Limitations of Coverage and/or Medical

Necessity” section of the LCD to add the following indication: estrogen positive breast carcinoma with 1-3 positive nodes. The effective date of this revision is based on date of service.

Revision Number:Original

Start Date of Comment Period:N/A Start Date of Notice Period:12/04/2008 Revised Effective Date:02/16/2009

LCR A2009-

December 2008 Bulletin

This LCD consolidates and replaces all previous policies and publications on this subject by the fiscal intermediary predecessors of First Coast Service Options, Inc. (COSVI and FCSO).

For Florida (00090) this LCD (L28849) replaces LCD L28088 as the policy in notice. This document (L28849) is effective on 02/16/2009.

8/1/2010 - The description for Bill Type Code 12 was changed 8/1/2010 - The description for Bill Type Code 13 was changed 8/1/2010 - The description for Bill Type Code 14 was changed 8/1/2010 - The description for Bill Type Code 85 was changed

8/1/2010 - The description for Revenue code 0301 was changed

Reason for Change Coverage Change (actual change in medical parameters)