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Date Printed: December 16, 2017: 09:26 PM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J2000-84

Original Effective Date: 09/15/17

Reviewed: 08/09/17

Revised: 00/00/00

Next Review: 09/12/18

Subject: Brigatinib (Alunbrig)

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.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates    
           

DESCRIPTION:

Lung cancer is the leading cause of cancer death in the United States. Approximately 222,000 new cases of lung cancer are predicted to be diagnosed in the United States in 2017. Lung cancer is divided into two major classes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for more than 85% of all lung cancers. Additionally, all lung cancers are evaluated for mutations or gene rearrangements – it is estimated that two to seven percent of patients with NSCLC have anaplastic lymphoma kinase (ALK) gene rearrangements.

Brigatinib (Alunbrig), a tyrosine kinase inhibitor, was approved by the U.S. Food and Drug Administration (FDA) in April 2017 for the treatment of patients with metastatic ALK-positive NSCLC who have progressed on or are intolerant to crizotinib. This indication was approved under accelerated approval based on tumor response rate and duration of response; continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The safety and efficacy of brigatinib were evaluated in subjects with locally advanced or metastatic ALK-positive NSCLC who had progressed on crizotinib in a non-comparative, two-arm, open-label, multicenter clinical trial (ALTA Trial; NCT02094573). All patients had tumors with a documented ALK rearrangement based on an FDA-approved test or a different test with adequate archival tissue to confirm ALK arrangement by the Vysis® ALK Break-Apart fluorescence in situ hybridization Probe Kit test. A total of 222 patients were randomized to brigatinib orally either 90 mg once daily (n=112) or 180 mg once daily following a 7-day lead-in at 90 mg once daily (n=110).

ORR was 48% (95% CI: 39%, 58%) in the 90 mg arm and 53% (95% CI: 43%, 62%) in the 180 mg arm. After a median duration of follow-up of 8 months, median duration of response (DOR) was 13.8 months in both arms. In patients with measurable brain metastases at baseline, intracranial ORR was 42% (95% CI: 23%, 63%) in the 90 mg arm (n=26) and 67% (95% CI: 41%, 87%) in the 180 mg arm (n=18). Median intracranial DOR was not estimable in the 90 mg arm and was 5.6 months in the 180 mg arm. Among patients who exhibited an intracranial response, 78% of patients in the 90 mg arm and 68% of patients in the 180 mg arm maintained an intracranial response for at least 4 months.

Safety was evaluated in 219 patients who received at least one dose of brigatinib in the ALTA trial. The most common adverse reactions, occurring in at least 25% of patients taking brigatinib, were nausea, diarrhea, fatigue, cough, and headache. The most common serious adverse reactions were pneumonia and ILD/pneumonitis. Fatal adverse reactions occurred in 3.7% of patients and consisted of pneumonia (2 patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis and urosepsis (1 patient each). Visual disturbances also occurred in patients receiving brigatinib. Adverse reactions leading to permanent discontinuation of brigatinib occurred in 2.8% and 8.2% of patients receiving 90 mg and 180 mg, respectively.

Patients receiving brigatinib should be monitored for new or worsening respiratory symptoms, hypertension, bradycardia, visual symptoms, and elevations in amylase, lipase, blood glucose, and creatine phosphokinase.

National Comprehensive Cancer Network (NCCN) Guidelines for Non-Small Cell Lung Cancer (Version 8.2017) recommend brigatinib as single-agent therapy for ALK rearrangement-positive recurrent or metastatic disease following progression on crizotinib or for patients intolerant to crizotinib.

POSITION STATEMENT:

Comparative Effectiveness

The FDA has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

Initiation of brigatinib (Alunbrig) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with recurrent or metastatic non-small cell lung cancer

2. Member has anaplastic lymphoma kinase (ALK)-positive disease – laboratory documentation must be provided

3. Brigatinib will be used as either of the following:

a. Subsequent therapy following disease progression on first-line therapy with crizotinib (Xalkori)

b. For members who are intolerant to crizotinib (Xalkori)

4. Brigatinib will be used as monotherapy

5. Dose does not exceed 180 mg daily – dosage will be achieved using the fewest number of tablets per day

Approval duration: 6 months

Continuation of brigatinib (Alunbrig) 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 NSCLC, OR the member has previously met all indication-specific criteria

2. Brigatinib is used as monotherapy

3. Member’s disease has not progressed during treatment with brigatinib

4. Dose does not exceed 180 mg daily – 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

• 90 mg orally once daily for the first 7 days; if tolerated, increase to 180 mg orally once daily

• May be taken with or without food.

Dose Adjustments

• Refer to product label

Drug Availability

• Tablets: 30 mg and 90 mg

PRECAUTIONS:

Boxed Warning

• None

Contraindications

• None

Precautions/Warnings

• Interstitial Lung Disease (ILD)/Pneumonitis: Occurred in 9.1% of patients at the recommended dose.

• Hypertension

• Bradycardia

• Visual Disturbance

• Creatine Phosphokinase (CPK) Elevation

• Pancreatic Enzyme Elevation

• Hyperglycemia

• Embryo-Fetal Toxicity: Can cause fetal harm.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J8999

Prescription drug, oral, chemotherapeutic, Not Otherwise Specified

ICD-10 Diagnoses Codes That Support Medical Necessity

C33

Malignant neoplasm of trachea

C34.00 – C34.92

Malignant neoplasm of bronchus and lung

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

DEFINITIONS:

No guideline specific definitions apply.

RELATED GUIDELINES:

Crizotinib (Xalkori®) Capsules, 09-J1000-57

OTHER:

None.

REFERENCES:

  1. Ariad. Alunbrig (brigatinib) tablet, coated. 2017 [cited 7/27/17]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07b71b73-1ca3-4e78-a787-e458917f1f23.
  2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2015 [cited 7/27/17]. Available from: http://www.clinicalpharmacology.com/.
  3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 7/27/17]. Available from: http://clinicaltrials.gov/.
  4. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 7/27/17]. Available from: http://www.thomsonhc.com/.
  5. Kim DW, Tiseo M, Ahn MJ, et al. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial. J Clin Oncol. 2017 Aug 1;35(22):2490-2498
  6. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Non-small cell lung cancer, v. 8.2017 [cited 7/27/17]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  7. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2017 [cited 7/27/17]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  8. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2015 [cited ????. 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 08/09/17.

GUIDELINE UPDATE INFORMATION:

09/15/17

New Medical Coverage Guideline.

Date Printed: December 16, 2017: 09:26 PM