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09-J1000-47

Original Effective Date: 01/01/12

Reviewed: 03/08/17

Revised: 04/15/17

Subject: Lapatinib (Tykerb®) Tablet

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           

Position Statement

Dosage/ Administration

Billing/Coding

Reimbursement

Program Exceptions

Definitions

           

Related Guidelines

Other

References

Updates

 

Previous Version

           

DESCRIPTION:

Lapatinib (Tykerb) is an oral oncology agent indicated for treatment of advanced or metastatic breast cancer that is hormone-receptor positive and or human epidermal receptor Type 2 (HER)-positive. The HER tyrosine kinase receptor family includes four transmembrane receptors (HER1/epidermal growth factor receptor [EGFR], HER2, HER3, and HER4) that mediate cell growth, survival, and differentiation. HER receptors activate intracellular signaling pathways. In 20% to 30% of breast tumors, the HER2 gene is amplified and overexpressed, leading to altered regulation of tumor cell growth, proliferation, and survival. Lapatinib is one of four commercially available anti-HER2 therapies.

Current National Comprehensive Cancer Network (NCCN) guidelines for the treatment of recurrent or stage IV (metastatic) breast cancer focus on prolonging survival, alleviating symptoms, and maintaining or improving quality of life. Persons in this stage are initially stratified according to whether bone metastasis is present. These two subsets are then stratified further by tumor hormone receptor (estrogen-receptor [ER] or progesterone-receptor [PR]) and HER2 status. NCCN guidelines support the use of lapatinib in the following settings:

• Recurrent or metastatic breast cancer that is ER-positive/HER2-positive when lapatinib is used in combination with an aromatase inhibitor (in biological males, also in combination with an agent that suppresses testicular steroidogenesis)

• Recurrent or metastatic breast cancer that is HER2-positive as second-line therapy (i.e., following trastuzumab [Herceptin]) when lapatinib is used in combination with either trastuzumab or capecitabine (Xeloda)

• Brain metastasis secondary to breast cancer when lapatinib is used in combination with capecitabine and the primary tumor (breast) was responsive to lapatinib therapy

Lapatinib has not been studied in combination with other anti-HER2 therapies (i.e., pertuzumab [Perjeta] and ado-trastuzumab emtansine [Kadcyla]). Additionally, while NCCN categorizes the use of lapatinib following trastuzumab exposure in the treatment of HER2-positive recurrent or metastatic breast cancer as a 2A recommendation, ado-trastuzumab emtansine is listed as the preferred therapy in this setting. This recommendation is based on results from the EMILIA study, which evaluated ado-trastuzumab emtansine versus lapatinib plus capecitabine for the treatment of unresectable locally advanced or metastatic HER2-positive breast cancer. The primary efficacy endpoints were progression-free survival (PFS) and overall survival (OS). The PFS in the ado-trastuzumab emtansine-treated group was extended by 3.2 months when compared to that of the comparator arm (9.6 months vs. 6.4 months, respectively; HR=0.65, 95% CI 0.55-0.77, p<0.001). The median OS was also significantly greater in subjects randomized to the ado-trastuzumab group compared to that of the comparator arm (30.9 months vs. 25.1 months, respectively; HR=0.68, 95% CI 0.55-0.85, p<0.001).

POSITION STATEMENT:

Initiation of lapatinib (Tykerb) meets the definition of medical necessity for members diagnosed with ANY of the following conditions when ALL associated criteria are met:

1. Breast Cancer

a. Member is diagnosed with recurrent or metastatic disease

b. Member has HER2-positive disease as documented by ONE of the following – laboratory documentation must be provided:

i. Immunohistochemistry (IHC) is 3+

ii. Fluorescent in situ hybridization (FISH) HER2 gene copy is greater than 6

iii. FISH ratio of HER2 gene/chromosome 17 ratio is greater than or equal to 2.0

c. Member meets ONE of the following:

i. ER-positive disease – laboratory documentation must be provided

• Member received prior trastuzumab (Herceptin) therapy AND lapatinib will be used in combination with trastuzumab (Herceptin) or capecitabine (Xeloda)

• Member is postmenopausal AND lapatinib will be used in combination with an aromatase inhibitor (e.g., letrozole)

• Lapatinib will be used in combination with an aromatase inhibitor and an agent that suppresses testicular steroidogenesis (e.g., leuprolide, goserelin)

ii. ER- or PR-negative disease – laboratory documentation must be provided

• Member received prior trastuzumab (Herceptin) therapy AND lapatinib will be used in combination with trastuzumab (Herceptin) or capecitabine (Xeloda)

d. Dose does not exceed 1,500 mg/day – dosage will be achieved using the fewest number of tablets per day

2. Brain Metastases

a. Lapatinib was active against primary tumor (i.e., breast)

b. Lapatinib will be used in combination with capecitabine (Xeloda)

c. Dose does not exceed 1,500 mg/day – dosage will be achieved using the fewest number of tablets per day

Approval duration: 6 months

Continuation of lapatinib (Tykerb) meets the definition of medical necessity when ALL of the following criteria are met:

1. Authorization/reauthorization has been previously approved by Florida Blue or another health plan in the past two years for treatment of breast cancer or brain metastases, OR the member has previously met all indication-specific initiation criteria

2. Dose does not exceed 1,500 mg/day – dosage will be achieved using the fewest number of tablets per day

Approval duration: 6 months

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved indications

1. In combination with capecitabine for the treatment of advanced or metastatic breast cancer that is HER2 positive following prior therapy including an anthracycline, a taxane, and trastuzumab

2. In combination with letrozole for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that is HER2 positive

Recommended dosing

The recommended dosing is listed in table 1. Lapatinib should be administered at least one hour before or one hour after a meal. Lapatinib should be administered once daily and the daily dose should not be divided.

Table 1

FDA-approved dosing

In combination with capecitabine

1,250 mg (5 tablets) once daily on days 1-21 of a 21 day cycle

In combination with letrozole

1500 mg (6 tablets) once daily

Dosage modifications

The lapatinib dose should be adjusted for cardiac and other toxicities, severe hepatic impairment, diarrhea, and CYP3A4 drug interactions. Table 2 outlines recommended dose modifications.

Table 2

Lapatinib dose modifications

Toxicity/Adverse Effect/Drug Interaction

Recommendation

Cardiac Events-decrease in LVEF that is Grade 2 or greater by NCI CTCAE OR below institutions lower limit of normal

Following a minimum of 2 weeks after LVEF recovers to normal and member is asymptomatic:

• In combination with capecitabine: reduce dose to 1000 mg/day

• In combination with letrozole: reduce dose to 1250 mg/day

Hepatic Impairment: Child-Pugh Class C

• HER2 positive MBC: reduce dose to 750 mg/day

• Hormone receptor positive/HER2 positive: reduced dose to 1000 mg/day

Diarrhea: NCI CTCAE Grade 3 or Grade 1 or 2 with complicating features

• Interrupt dosing

• Reinitiate at a lower dose once diarrhea resolves to Grade 1 or less

o HER2 positive MBC: reduce dose to 1000 mg/day

o Hormone receptor positive/HER2 positive: reduced dose to 1250 mg/day

Diarrhea: NCI CTCAE Grade 4

Discontinue permanently

Concomitant Strong CYP3A4 Inhibitor

Avoid is possible; if coadministration is unavoidable, reduce lapatinib dose to 500 mg/day

Concomitant Strong CYP3A4 Inducer

Avoid if possible; if coadministration is unavoidable, lapatinib dose should be titrated gradually:

• HER2 positive MBC: from 1250 mg/day to 4500 mg/day

• Hormone receptor positive/HER2 positive: 1500 to 5500 mg/day

Other toxicities

• Discontinue to interrupt lapatinib may be considered in members who develop Grad 2 or higher NCI CTCAE toxicity and can be restarted at 1250 mg/day when toxicity improves to Grade 1 or less.

• If toxicity recurs, the dose should be reduced to 1000 mg/day when used in combination with capecitabine and 1250 mg/day when used in combination with letrozole.

LVEF, left ventricular ejection fraction; NCI CTCAE, National Cancer Institute Common Technology Criteria for adverse events

Drug Availability: lapatinib is supplied as a 250 mg tablet.

PRECAUTIONS:

Boxed Warning:

Hepatotoxicity has been observed in clinical trials and postmarketing experience. The hepatotoxicity may be serve and deaths have been reported. Causality of death is uncertain.

Contraindications:

Lapatinib is contraindicated in persons with known severe hypersensitivity (e.g., anaphylaxis) to lapatinib or any of its components.

Precautions/Warnings:

• Decreases in left ventricular ejection fraction have been reported. Confirm normal LVEF before starting lapatinib and continue evaluations during treatment.

• Lapatinib has been associated with hepatotoxicity. Monitor liver function tests before initiation of treatment, every 4 to 6 weeks during treatment, and as clinically indicated. Discontinue and do not restart lapatinib if member experiences severe changes in liver function tests.

• Dose reduction in members with severe hepatic impairment should be considered.

• Diarrhea, including severe diarrhea, has been reported during treatment. Manage with anti-diarrheal agents, and replace fluids and electrolytes if severe.

• Lapatinib has been associated with interstitial lung disease and pneumonitis. Discontinue lapatinib if member experiences severe pulmonary symptoms.

• Lapatinib may prolong the QT interval in some individuals. Consider ECG and electrolyte monitoring.

• Fetal harm can occur when administered to a pregnant woman. Women should be advised not to become pregnant when taking lapatinib

BILLING/CODING INFORMATION:

HCPCS Coding

J8999

Prescription drug, oral, chemotherapeutic, NOS

ICD-10 Diagnoses Codes That Support Medical Necessity

C15.3 – C15.9

Malignant neoplasm of esophagus

C16.0 – C16.9

Malignant neoplasm of the stomach

C50.011 – C50.929

Malignant neoplasm of breast

C79.31

Secondary malignant neoplasm of brain

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

DEFINITIONS:

No guideline specific definitions apply.

RELATED GUIDELINES:

Capecitabine (Xeloda®) Tablets, 09-J1000-42
Docetaxel (Taxotere®) IV, 09-J0000-95

Fulvestrant (Faslodex®) IM, 09-J1000-04

Gemcitabine (Gemzar®), 09-J0000-96

Gonadotropin Releasing Hormone Analogs and Antagonists, 09-J0000-48

Paclitaxel and Paclitaxel (protein-bound) IV, 09-J1000-05

Positron Emission Tomography (PET Scans) Oncologic Applications, 04-78000-17

Proton Beam Therapy, 04-77260-18

Trastuzumab (Herceptin®) Injection, 09-J0000-86

Vinorelbine Tartrate (Navelbine®) IV, 09-J1000-03

OTHER:

None

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2015 [cited 2015 Jan 28]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited2017 Jan 28]. Available from: http://www.clinicalpharmacology.com/.
  3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2017 Jan 28]. Available from: http://clinicaltrials.gov/.
  4. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017 Jan 28]. Available from: http://www.thomsonhc.com/.
  5. Tykerb (lapatinib)[package insert]. GlaxoSmithKline LLC. Research Triangle Park (NC): October 2013.
  6. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2017 [cited 2017 Jan 28]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  7. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017 Jan 28]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 03/08/17.

GUIDELINE UPDATE INFORMATION:

01/01/12

New Medical Coverage Guideline.

11/15/12

Review and revision to guideline; consisting of updating position statement, added contraindication, updated precautions and warnings, coding, program exceptions, related guidelines and references.

12/15/13

Review and revision to guideline; consisting of revising position statement, revising description section, dosage/administration section, precaution section, and updating references.

04/15/14

Review and revision to guideline; consisting of reformatting position statement and updating references.

04/15/15

Review and revision to guideline; consisting of position statement, dosage/administration, program exceptions, references.

11/01/15

Revision: ICD-9 Codes deleted.

04/15/16

Review and revision; position statement, coding, references.

04/15/17

Review and revision; position statement,description, references.

Date Printed: June 23, 2017: 11:39 AM