Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Trastuzumab (Herceptin®) and Related Biosimilars

Policy #:08.00.33l

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin 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 Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

Trastuzumab (Herceptin®) and related biosimilars (e.g., trastuzumab-dkst [Ogivri]) are considered medically necessary and, therefore, covered in individuals with breast, gastric, advanced esophageal, or gastroesophageal cancer whose tumors have human epidermal growth factor receptor 2 (HER2) protein overexpression and who meet the criteria listed below. HER2 protein overexpression must be verified as a positive result by one of the following FDA-approved diagnostic tests:
  • Immunohistochemical (IHC) assay with a result of 3+
  • Fluorescence in situ hybridization (FISH) test (ratio greater than 2.0)
  • Single-probe in situ hybridization (ISH) test with average HER2 copy number 6.0 signals/cell or greater
  • Dual-probe ISH test HER2/CEP17 (chromosome enumeration probe 17) ratio 2.0 or greater; or HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 6.0 signals/cell or greater
Confirmatory tests should be performed for borderline results as follows:
  • If IHC assay has a result of 2+, confirm with ISH test of the same sample or a new test with IHC or ISH (if new sample available).
  • If FISH test has a HER2 gene/chromosome 17 ratio of 1.8-2.0, confirm with FISH re-test; additional cell counting and recalculation of the ratio; or IHC assay.
  • If single-probe ISH assay has an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available).
  • If dual-probe ISH assay has a HER2/CEP17 ratio less than 2.0 and an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).

BREAST CANCER
  • Adjuvant treatment of individuals with HER2 overexpressing node-positive or node-negative (estrogen receptor/progesterone receptor--negative or with one high-risk feature) breast cancer, as part of any of the following treatment regimens:
    • In combination with AC (doxorubicin and cyclophosphamide) and either paclitaxel or docetaxel
      • Preferred regimen per NCCN (National Comprehensive Cancer Network) is trastuzumab with paclitaxel following AC regimen
    • In TCH (docetaxel, carboplatin, and trastuzumab) regimen as an NCCN-preferred regimen
    • As a single agent following multi-modality anthracycline-based therapy
  • Adjuvant treatment of individuals with HER2-positive stage I, IIA, IIB, or IIIA (T3, N1, M0) disease (ductal, lobular, mixed, or metaplastic histologies), or for locally advanced disease (stage IIIA (any T, N2, M0), IIIB, or IIIC).
    • In combination with paclitaxel following AC (doxorubicin and cyclophosphamide) regimen as an NCCN-preferred regimen
    • In TCH (docetaxel, carboplatin, and trastuzumab) regimen as an NCCN-preferred regimen
    • In combination with docetaxel following AC (doxorubicin and cyclophosphamide) regimen
    • In combination with docetaxel and cyclophosphamide
    • In TCH regimen (as an NCCN-preferred regimen) with pertuzumab (Perjeta®)
    • In combination with pertuzumab (Perjeta®) and paclitaxel (as an NCCN-preferred regimen) or pertuzumab (Perjeta®) and docetaxel following AC regimen
  • Adjuvant treatment of individuals with HER2-positive, low-risk stage I breast cancer
    • In combination with paclitaxel (particularly for individuals not eligible for other standard adjuvant regimens due to comorbidities)
  • Adjuvant treatment of individuals with HER2-positive early breast cancer at high risk of recurrence in combination with pertuzumab (Perjeta®) and chemotherapy
  • Preoperative (neoadjuvant) chemotherapy for individuals with HER2-positive breast cancer:
    • In those who have locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive):
      • In combination with pertuzumab (Perjeta®) and chemotherapy
    • In those who have stage stage IIA (T0, N1, M0 or T1, N1, M0 or T2, N0, M0), stage IIB (T2, N1, M0 or T3, N0, M0), or stage IIIA (T3, N1, M0) breast cancer who desire breast preservation and fulfill the criteria for breast-conserving surgery, except for tumor size, or for those who have node-positive disease likely to become node-negative with preoperative systemic therapy, or for individuals with locally advanced disease (stage IIIA (any T, N2, M0), IIIB, or IIIC):
      • Concurrently with paclitaxel following AC (doxorubicin and cyclophosphamide) regimen as an NCCN-preferred regimen with or without pertuzumab (Perjeta®)
      • In TCH (docetaxel, carboplatin, and trastuzumab) regimen with or without pertuzumab (Perjeta®) as an NCCN-preferred regimen
      • In combination with docetaxel with or without pertuzumab (Perjeta®) following AC regimen
      • In combination with docetaxel and cyclophosphamide
  • Metastatic or recurrent breast cancer treatment:
    • As a single agent for the treatment of HER2-overexpressing breast cancer in individuals who have received one or more chemotherapy regimens metastatic disease
    • In combination with tamoxifen, fulvestrant, or aromatase inhibitors (e.g., anastrozole [Arimidex®], exemestane [Aromasin®], letrozole [Femara®)] with or without lapatinib for the treatment of recurrent or stage IV estrogen receptor-positive, HER2-positive disease in postmenopausal women*
    • In combination with tamoxifen for the treatment of recurrent or stage IV estrogen receptor-positive, HER2-positive disease in premenopausal women*
        *Men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis
    • In combination with pertuzumab (Perjeta®) and docetaxel for the treatment of individuals with HER2-positive disease who have not received prior anti-HER2 therapy or chemotherapy
    • For individuals with HER2-positive recurrent or metastatic breast cancer that is either hormone receptor-negative, hormone receptor-positive and endocrine therapy refractory, with symptomatic visceral disease, or visceral crisis:
      • First-line therapy in combination with pertuzumab (Perjeta®) with docetaxel or paclitaxel as an NCCN-preferred regimen
      • In combination with docetaxel, vinorelbine, or capecitabine; or with paclitaxel with or without carboplatin
      • Treatment for trastuzumab-exposed HER2-positive disease in combination with lapatinib (without cytotoxic therapy), capecitabine, carboplatin, cyclophosphamide, eribulin, gemcitabine, ixabepilone, paclitaxel, docetaxel, vinorelbine, or albumin-bound paclitaxel
      • In combination with pertuzumab (Perjeta®) with or without cytotoxic therapy (e.g., vinorelbine or taxane) for one line of therapy beyond first-line therapy in individuals previously treated with chemotherapy and trastuzumab in the absence of pertuzumab (Perjeta®)

CENTRAL NERVOUS SYSTEM METASTASES
  • Leptomeningeal metastases from breast cancer, intracerebrospinal fluid (CSF) treatment
    • Primary treatment of individuals with normal CSF flow or no clinical evidence of abnormal flow
    • As maintenance therapy for individuals with negative CSF cytology or for clinically stable individuals with persistently positive CSF cytology
    • Therapy for individuals with positive CSF cytology

GASTRIC AND GASTROESOPHAGEAL CANCERS
  • Metastatic gastric cancer, esophageal cancer, or esophagogastric junction cancer:
    • For the palliative treatment of individuals with Karnofsky performance score of 60% or greater, or ECOG performance score of 2 or less who have advanced HER2 protein overexpressing gastric adenocarcinoma, esophageal adenocarcinoma, or esophagogastric junction adenocarcinoma:
      • In combination with cisplatin and either fluorouracil or capecitabine as first-line therapy

EXPERIMENTAL/INVESTIGATIONAL

All other uses of trastuzumab (Herceptin®) and related biosimilars (e.g., trastuzumab-dkst [Ogivri]) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company's medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

Refer to Attachment A for dosing and frequency requirements for trastuzumab (Herceptin®) and related biosimilars (e.g., trastuzumab-dkst [Ogivri]).

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this Policy to ensure consistency with the most recently published recommendations for the use of trastuzumab (Herceptin®) and related biosimilars. Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA), Company-recognized authoritative pharmacology compendia, or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of trastuzumab and related biosimilars outside of the Dosing and Frequency Requirements listed in this Policy. For a list of Company-recognized pharmacology compendia, view the policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for trastuzumab and related biosimilars.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The Eastern Cooperative Oncology Group (ECOG), established in 1955, was one of the first groups to coordinate multicenter cancer clinical trials. The National Cancer Institute (NCI) is the primary funding source, and ECOG has evolved from a small consortium of institutions in the eastern United States to one of the largest clinical cancer research organizations in the country. As part of their work in the treatment of cancer, ECOG has developed the ECOG Performance Status (EPS), originally published in 1982 in the American Journal of Clinical Oncology. The use of the scales and the criteria in the EPS allows clinicians and researchers to determine an individual’s disease progression in terms of how the activities of daily living (ADL) are affected.

ECOG Performance Status
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work)
2
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3
Capable of only limited self care, confined to bed or chair more than 50 percent of waking hours
4
Completely disabled. Cannot carry on any self care: Totally confined to bed or chair
5
Dead
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.


THE KARNOFSKY PERFORMANCE STATUS

The Karnofsky Performance Status (KPS) is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. Performance scores range from 0 to 100; a higher score indicates that the individual is better able to perform activities. KPS may be used to determine an individual's prognosis, to measure changes in an individual's ability to function, or to decide if an individual can participate in a clinical trial.

The Karnofsky Performance Status Scale
100 percentNormal, no complaints; no signs of disease
90 percentCapable of normal activity; few symptoms or signs of disease
80 percentNormal activity with some difficulty; some symptoms or signs of disease
70 percentCaring for self; not capable of normal activity or work
60 percentRequiring some help; can take care of most personal requirements
50 percentRequires help often; requires frequent medical care
40 percentDisabled; requires special care and help
30 percentSeverely disabled, but no risk of death
20 percentVery ill; requires supportive measures or treatment
10 percentMoribund; rapidly progressive fatal disease processes
0 percentDeath


BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, trastuzumab (Herceptin®) is covered under the medical benefits of the Company’s products when the medical necessity criteria and dosing and frequency requirements listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA)

The FDA granted initial approval for the use of trastuzumab (Herceptin®) to Genentech, Inc. (South San Francisco, CA) on September 25, 1998; supplemental approvals have since been issued.

The FDA granted initial approval for the use of trastuzumab-dkst (Ogivri) to Mylan GmbH (Morgantown, WV) on December 1, 2017.

Description

Trastuzumab (Herceptin®) and related biosimilars (e.g., trastuzumab-dkst [Ogivri]), which are monoclonal antibodies that bind to human epidermal growth factor receptor 2 (HER2, previously called HER2/neu) protein, are used to treat individuals with breast or gastric cancer whose tumors overexpress the HER2 protein. The HER2 gene is found on chromosome 17 and is involved in the process for making the HER2 protein. The HER2 protein is a receptor on the surface of the cell and sends messages to the cell to grow and divide more frequently. When cells have more than the normal number of copies of the HER2 gene, the gene is called amplified. Amplification of the HER2 gene results in HER2 protein overexpression, which occurs in approximately 25 percent of breast and gastric cancer cases. HER2 gene amplification and HER2 protein overexpression are highly correlated with faster tumor growth, shortened disease-free survival time, and shortened overall survival for individuals with breast or gastric cancer. Trastuzumab (Herceptin®) and related biosimilars are designed to target and block HER2 activity. Trastuzumab (Herceptin®) and related biosimilars are supplied as sterile lyophilized powders and are administered by intravenous (IV) infusion.

BREAST CANCER TREATMENT

METASTATIC BREAST CANCER TREATMENT
The US Food and Drug Administration (FDA) approved the uses of trastuzumab (Herceptin®) and related biosimilars for the treatment of individuals with metastatic breast cancer whose tumors overexpress the HER2 protein in any of the following regimens:
  • In combination with paclitaxel in those who have not received chemotherapy for metastatic disease
  • As a single agent for individuals who have previously received chemotherapy for metastatic disease
  • In combination with pertuzumab (Perjeta®) and docetaxel (Taxotere®) for those who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease

Trastuzumab (Herceptin®) and related biosimilars (e.g., trastuzumab-dkst [Ogivri]) were studied for use in the initial treatment of HER2-overexpressing metastatic breast cancer in combination with an anthracycline and cyclophosphamide. However, in a large, randomized, clinical trial, the clinical benefits did not outweigh the increased risk of serious cardiac toxicity. Therefore, the FDA did not grant approval for the use of trastuzumab (Herceptin®) in combination with anthracycline and cyclophosphamide.

ADJUVANT BREAST CANCER TREATMENT
Trastuzumab (Herceptin®) and related biosimilars (e.g., trastuzumab-dkst [Ogivri]) have been studied for use as adjuvant treatment, which is therapy given after the primary treatment to increase the chances of a cure. Since 2006, the FDA has approved the use of trastuzumab (Herceptin®) in the adjuvant setting for the treatment of individuals with HER2-overexpressing breast cancer in specific chemotherapy regimens.

The use of trastuzumab (Herceptin®) and related biosimilars in the adjuvant setting was supported by three large Phase 3 randomized controlled trials (RCTs). The National Cancer Institute (NCI) sponsored two large Phase 3 RCTs that studied the use of trastuzumab (Herceptin®) in combination with standard chemotherapy as an adjuvant to complete surgical resection in early-stage HER2-overexpressing breast cancer. The results of the interim analysis showed that individuals who received trastuzumab (Herceptin®) in addition to chemotherapy experienced a significant increase in disease-free survival time, as well as a significant reduction in the relative risk of recurrence compared with those who received chemotherapy alone. Based on the significance of these findings, the two trials were stopped, as the studies had met their primary endpoints, and the committees overseeing the trial data recommended that the interim analysis be made public. This data was presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in May 2005 and published in the New England Journal of Medicine in October 2005. A third large Phase 3 RCT that studied trastuzumab (Herceptin®) as adjuvant chemotherapy was the international HERceptin Adjuvant (HERA) trial. Interim data from the HERA trial that demonstrated a statistically significant increase in disease-free survival time at two years was also presented at the ASCO meeting in 2005.

NEOADJUVANT BREAST CANCER TREATMENT
Neoadjuvant therapy is treatment given before the primary treatment (e.g., preoperatively). Trastuzumab (Herceptin®) and related biosimilars are recognized as an appropriate medical treatment in the neoadjuvant setting when used preoperatively in combination with paclitaxel or docetaxel, followed in combination with the FEC/CEF regimen (fluorouracil, epirubicin, and cyclophosphamide); with paclitaxel or docetaxel following AC (doxorubicin and cyclophosphamide); or with docetaxel and carboplatin for individuals with breast cancer whose tumors overexpress the HER2 protein and meet additional criteria.

Trastuzumab (Herceptin®) and related biosimilars are also approved by the FDA for use in combination with pertuzumab (Perjeta®) and docetaxel (Taxotere®) for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer.

GASTRIC AND GASTROESOPHAGEAL JUNCTION CANCERS

Trastuzumab (Herceptin®) and related biosimilars (e.g., trastuzumab-dkst [Ogivri]) have been shown to improve survival in individuals with advanced gastric and gastroesophageal junction cancers in the international Phase 3 Trastuzumab for Gastric Cancer (ToGA) trial, which compared two treatments in 594 individuals whose tumors showed elevated levels of the HER2 protein. ToGA is the first randomized Phase 3 trial to study the use of trastuzumab (Herceptin®) in individuals who have inoperable locally advanced, recurrent, and/or metastatic HER2-positive gastric and gastroesophageal junction cancers. The results for this trial were presented at the American Society of Clinical Oncology (ASCO) 2009 annual meeting. The trial demonstrated that individuals who received chemotherapy alone lived 11.1 months, whereas those who received trastuzumab (Herceptin®) with chemotherapy lived 13.8 months. The response rate was increased with trastuzumab (Herceptin®) from 34.5 percent to 47.3 percent. In addition, individuals whose gastric and gastroesophageal junction cancers exhibited high levels of HER2 experienced even greater benefit from the addition of trastuzumab (Herceptin®) (16 months median survival). The chemotherapy arm of the trial consisted of a fluoropyrimidine (capecitabine or intravenous 5-fluorouracil [5-FU]) and cisplatin every three weeks for six cycles; the trastuzumab (Herceptin®) arm received trastuzumab (Herceptin®) every three weeks until disease progression in combination with a fluoropyrimidine and cisplatin for six cycles.

In October 2010, trastuzumab (Herceptin®) was approved by the US Food and Drug Administration for use in metastatic gastric and gastroesophageal junction adenocarcinomas.

OTHER CANCERS

Trastuzumab (Herceptin®) has been studied for use in other cancers (e.g., osteosarcoma, non-small cell lung, ovarian, prostate, head and neck, pancreatic, colorectal, endometrial, urothelial cancers); however, to date, many Phase 2 trials have failed to demonstrate the effectiveness of trastuzumab (Herceptin®). Also, some cancers show a low incidence of HER2 protein overexpression. Research is ongoing, and whether trastuzumab (Herceptin®) use will have an effect on health outcomes in other cancers is not yet determined.

DIAGNOSTIC TESTS FOR HER2 PROTEIN OVEREXPRESSION

HER2 protein overexpression is detected either by immunohistochemical (IHC) assay or with a type of in situ hybridization (ISH) test for gene amplification (e.g., fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], dual in situ hybridization [DISH]). The FDA has approved several commercially available tests to aid in the selection of breast cancer and metastatic gastric cancer patients for trastuzumab
(Herceptin®) therapy. Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using FDA-approved tests specifically for gastric cancers due to differences in gastric versus breast histopathology. The NCCN and ASCO guidelines further recommend that IHC assay and ISH testing should only be done at laboratories that are accredited to perform HER2 testing.
  • An IHC test result is reported as 0 or 1+ (negative), 2+ (borderline), or 3+ (positive).
  • A FISH test result is reported as a HER2 gene/chromosome 17 ratio less than 1.8 (negative), a ratio of 1.8 to less than 2.0 (borderline), or a ratio of 2.0 or greater (positive).
  • A single-probe ISH test result is reported as: average HER2 copy number less than 4.0 signals/cell (negative); 4.0 to less than 6.0 signals/cell (borderline); 6.0 or greater signals/cell (positive).
  • A dual-probe ISH test result is reported as HER2/CEP17 (chromosome enumeration probe 17) ratio 2.0 or greater (positive); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number less than 4.0 signals/cell (negative); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 4.0 to less than 6.0 signals/cell (borderline); HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 6.0 signals/cell or greater (positive).

The NCCN and ASCO both have issued guidelines for HER2 testing in invasive breast cancer that call for confirming a borderline or equivocal result:
  • IHC assay result of 2+: confirm with ISH test (if same sample), or with a new IHC or ISH test (if new sample available).
  • FISH assay: confirm with either a repeat FISH test or an additional cell counting and recalculation of the ratio. If a repeat FISH test remains equivocal, then an IHC assay is recommended for confirmation.
  • Single-probe ISH assay: confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available).
  • Dual-probe ISH assay: confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).

Trastuzumab (Herceptin®) and related biosimilars are not indicated in any type of cancer that does not overexpress the HER2 protein.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


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Hede K. Gastric cancer: Trastuzumab trial results spur search for other targets. J Nat Cancer Inst. 2009;101(19):1306-1307. Also available on the Journal of the National Cancer Institute Web site at: http://jnci.oxfordjournals.org/cgi/content/short/101/19/1306. Accessed January 12, 2018.

Hehl EM. Opinion on the use of the antitumor drug trastuzumab (Herceptin) in patients with metastatic breast cancer in the county Mecklenburg-Vorpommern. Int J Clin Pharmacol Ther. 2001;39(11):503-506.

Hind D, Pilgrim H, Ward S. Questions about adjuvant trastuzumab still remain. Lancet. 2007;369(9555):3-5.

Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Engl J Med. 2005;353(16):1734-1736.

Hurley J, Doliny P, Reis I, et al. Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol. 2006;24(12):1831-1838.

Hussain MH, MacVicar GR, Petrylak DP, et al. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. J Clin Oncol. 2007;25(16):2218-2224.

Jackisch C. HER2-positive metastatic breast cancer: optimizing trastuzumab-based therapy. Oncologist. 2006;11(suppl 1):34-41.

Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354(8):809-820.

Karnofsky performance scale. [Stall Geriatrics Web site]. 09/20/97. Available at: http://www.acsu.buffalo.edu/~drstall/karnofsky.html . Accessed January 12, 2018.

Krug LM, Miller VA, Patel J, et al. Randomized phase II study of weekly docetaxel plus trastuzumab versus weekly paclitaxel plus trastuzumab in patients with previously untreated advanced nonsmall cell lung carcinoma. Cancer. 2005;104(10):2149-2155.

Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17(2):460-469.

Langer CJ, Stephenson P, Thor A, et al. Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a role? Focus on Eastern Cooperative Oncology Group study 2598. J Clin Oncol. 2004;22(7):1180-1187.

Lara PN Jr, Chee KG, Longmate J, et al. Trastuzumab plus docetaxel in HER2/neu-positive prostate carcinoma: final results from the California Cancer Consortium Screening and Phase II Trial. Cancer. 2004;100(10):2125-2131.

Lara PN Jr, Meyers FJ, Gray CR, et al. HER2/neu is overexpressed infrequently in patients with prostate carcinoma. Results from the California Cancer Consortium Screening Trial. Cancer. 2002;94(10):2584-2589.

Micromedex® 2.0. DrugDex®. Trastuzumab (Herceptin®). [Micromedex 2.0 Web site]. 12/06/2017. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed January 12, 2018.

Miller KD, Sisk J, Ansari R, et al. Gemcitabine, paclitaxel, and trastuzumab in metastatic breast cancer. Oncology (Williston Park). 2001;15(2 Suppl 3):38-40.

Montemurro F, Choa G, Faggiuolo R, et al. A phase II study of three-weekly docetaxel and weekly trastuzumab in HER2-overexpressing advanced breast cancer. Oncology. 2004;66(1):38-45.

Montemurro F, Choa G, Faggiuolo R, et al. Safety and activity of docetaxel and trastuzumab in HER2 overexpressing metastatic breast cancer: a pilot phase II study. Am J Clin Oncol. 2003;26(1):95-97.

Morris MJ, Reuter VE, Kelly WK, et al. HER2 profiling and targeting in prostate carcinoma. Cancer. 2002;94(4):980-986.

Mueller-Holzner E, Fink V, Frede T, Marth C. Immunohistochemical determination of HER2 expression in breast cancer from core biopsy specimens: a reliable predictor of HER2 status of the whole tumor. Breast Cancer Res Treat. 2001;69(1):13-19.

Nagourney RA. Gemcitabine plus cisplatin in breast cancer. Oncology (Williston Park). 2001;15(2 Suppl 3):28-33.

Nanda R. Targeting the human epidermal growth factor receptor 2 (HER2) in the treatment of breast cancer: recent advances and future directions. Rev Recent Clin Trials. 2007;2(2):111-116.

National Cancer Institute. Cancer Drug Information: Trastuzumab. [National Cancer Institute Web site]. Available at: http://www.cancer.gov/cancertopics/druginfo/trastuzumab. Accessed December 15, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Breast Cancer. V3.2017. [NCCN Web site]. 11/10/2017. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf [via free subscription]. Accessed December 15, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines/ in Oncology - Central Nervous System Cancers. V1.2017. [NCCN Web site].08/18/2017. Available at: http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf . Accessed December 15, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Esophageal and Esophagogastric Junction Cancer. V4.2017. [NCCN Web site]. 10/13/2017. Available at: http://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf . Accessed December 15, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Gastric Cancer. V5.2017. [NCCN Web site].10/13/2017. Available at: http://www.nccn.org/professionals/physician_gls/PDF/gastric.pdf. Accessed December 15, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Pertuzumab (Perjeta®). [NCCN Web site]. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=383. via subscription only]. Accessed December 21, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Trastuzumab (Herceptin®). [NCCN Web site]. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed December 15, 2017.

O’Shaughnessy J, Vukelja SJ, Marsland T, et al. Phase II trial of gemcitabine plus trastuzumab in metastatic breast cancer patients previously treated with chemotherapy: preliminary results. Clin Breast Cancer. 2002;(3 Suppl 1):17-20.

Osoba D, Burchmore M. Health-related quality of life in women with metastatic breast cancer treated with trastuzumab (Herceptin). Semin Oncol. 1999;26(4 Suppl 12):84-88.

Pegram MD, Lipton A, Hayes DF, et al. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol. 1998;16(8):2659-2671.

Pegram MD, Pienkowski T, Northfelt DW, et al. Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer. J Natl Cancer Inst. 2004;96(10):759-769.

Pegram MD, Slamon DJ. Combination therapy with trastuzumab (Herceptin) and cisplatin for chemoresistant metastatic breast cancer: evidence for receptor-enhanced chemosensitivity. Semin Oncol. 1999;26(4 Suppl 12):89-95.

Persons DL, Bui MM, Lowery MC, et al. Fluorescence in situ hybridization (FISH) for detection of HER2/neu amplification in breast cancer: a multicenter portability study. Ann Clin Lab Sci. 2000;30(1):41-48.

Peyromaure M, Scotté F, Amsellem-Ouazana D, et al. Trastuzumab (Herceptin) in metastatic transitional cell carcinoma of the urinary tract: report on six patients. Eur Urol. 2005;48(5):771-778.

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659-1672.

Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-1684.

Ross JS, Fletcher JA. HER2/neu (c-erb-B2) gene and protein in breast cancer. Am J Clin Pathol. 1999;112(1 Suppl 1):S53-S67.

Safran H, Dipetrillo T, Akerman P, et al. Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2007;67(2):405-409.

Salzberg M, Borner M , Bauer JA, et al. Trastuzumab (Herceptin) in patients with HER2-overexpressing metastatic or locally advanced transitional cell carcinoma of the bladder: report on 7 patients. Eur J Cancer. 2006;42(15):2660-2661.

Seidman A, Hudis C, Pierri MK, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20(5):1215-1221.

Seidman AD, Fornier MN, Esteva FJ, et al. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol. 2001;19(10):2587-2595.

Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science. 1987;235(4785):177-182.

Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-792.

Small EJ, Bok R, Reese DM, et al. Docetaxel, estramustine, plus trastuzumab in patients with metastatic androgen-independent prostate cancer. Semin Oncol. 2001;28(4 Suppl 15):71-76.

Smith I, Procter 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;369(9555):29-36.

Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005;23(31):7811-7819.

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Zinner RG, Glisson BS, Fossella FV, et al. Trastuzumab in combination with cisplatin and gemcitabine in patients with Her2-overexpressing, untreated, advanced non-small cell lung cancer: report of a phase II trial and findings regarding optimal identification of patients with Her2-overexpressing disease. Lung Cancer. 2004;44(1):99-110.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment B


HCPCS Level II Code Number(s)

J9355 Injection, trastuzumab, 10 mg


THE FOLLOWING CODE IS USED TO REPRESENT TRASTUZUMAB-dkst (OGIVRI™):

J3590 Unclassified biologics



Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Trastuzumab (Herceptin®) and Related Biosimilars
Description: Dosing & Frequency Requirements for Trastuzumab (Herceptin®)

Attachment B: Trastuzumab (Herceptin®) and Related Biosimilars
Description: ICD-10 CM Codes and Narratives




Policy History

08.00.33l
03/09/2018This policy has undergone a routine review and the medical necessity criteria have been revised to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date: 03/09/2018
Version Issued Date: 03/09/2018
Version Reissued Date: N/A

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