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Date Printed: October 17, 2017: 04:16 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-J2000-17

Original Effective Date: 09/15/14

Reviewed: 09/13/17

Revised: 10/15/17

Subject: Ceritinib (Zykadia™) Capsules

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  

Previous Information

           

DESCRIPTION:

Lung cancer is the leading cause of cancer death in the United States; only 16% of all lung cancer patients are alive five years or more after diagnosis. 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. Crizotinib is a first-line treatment for patients with locally advanced or metastatic NSCLC who have ALK-positive disease.

Ceritinib (Zykadia), an orally active tyrosine kinase inhibitor of ALK that also inhibits the insulin-like growth factor-1 (IGF-1) receptor, was approved by the U.S. Food and Drug Administration (FDA) in April 2014 for the treatment of patients with ALK-positive metastatic 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; an improvement in survival or disease-related symptoms has not been established.

The safety and efficacy of ceritinib were evaluated in subjects (n=163) with metastatic ALK-positive NSCLC who progressed while receiving or were intolerant to crizotinib in a multicenter, single-arm, open-label clinical trial. All patients received ceritinib 750 mg once daily. The primary endpoint was objective response rate as evaluated by both investigators and a blinded independent central review committee (BIRC); duration of response was an additional outcome measure.

Efficacy results are summarized in table 1:

Table 1

Overall Response Rate and Duration of Response

Efficacy Parameter Parameter

Investigator Assessment

(N=163)

BIRC Assessment

(N=163)

Overall Response Rate (95% CI)

54.60% (47, 62)

43.60% (36, 52)

    CR

1.20%

2.50%

    PR

53.40%

41.10%

Duration of Response, median (months) (95% CI)

7.4 (5.4, 10.1)

7.1 (5.6, NE)

CR, complete response; NE, not estimable; PR, partial response.

Ceritinib has been associated with severe gastrointestinal toxicity, QTc interval prolongation, and bradycardia. The most frequently reported adverse events were diarrhea, nausea, and elevated transaminases. Administration with strong inhibitors, inducers, or substrates of CYP3A should be avoided.

National Comprehensive Cancer Network (NCCN) Guidelines for NSCLC (Version 8.2017) recommend ceritinib as a single agent for ALK-positive recurrent or metastatic disease.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration 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 ceritinib meets the definition of medical necessity when used for treatment of ANY of the following indications and ALL associated criteria are met:

  1. Non-small cell lung cancer (NSCLC)

a. Member’s disease is recurrent or metastatic

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

c. Ceritinib will be used as monotherapy

d. Ceritinib dose does not exceed 750 mg once daily – dosage will be achieved using the fewest number of capsules per day

  1. Inflammatory myofibroblastic tumor (IMT)

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

b. Ceritinib will be used as monotherapy

c. Ceritinib dose does not exceed 750 mg once daily – dosage will be achieved using the fewest number of capsules per day

Duration of approval: 6 months

Continuation of ceritinib 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 IMT that is ALK-positive, OR the member has previously met all indication-specific initiation criteria
  2. Ceritinib is used as monotherapy
  3. Ceritinib dose does not exceed 750 mg once daily – dosage will be achieved using the fewest number of capsules per day

Duration of approval: 1 year

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

• 750 mg orally once daily

Dose Adjustments

Strong CYP3A4 inhibitors: reduce dose by one-third, rounded to the nearest multiple of the 150 mg dosage strength

Recommendations for dose modifications due to adverse reactions are provided in FDA-approved Prescribing Information

Drug Availability

Capsules: 150 mg

PRECAUTIONS:

Boxed Warning

None

Contraindications

None

Precautions/Warnings

• Severe or Persistent Gastrointestinal Toxicity: Dose modification due to diarrhea, nausea, vomiting or abdominal pain occurred in 38% of patients

• Hepatotoxicity: Monitor liver laboratory tests at least monthly

• Interstitial Lung Disease (ILD)/Pneumonitis: Occurred in 4% of patients

• QT Interval Prolongation: Monitor electrocardiograms and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or those who are taking medications that are known to prolong the QTc interval

• Hyperglycemia: Monitor glucose and initiate or optimize anti-hyperglycemic medications as indicated

• Bradycardia: Monitor heart rate and blood pressure regularly

• Embryofetal Toxicity

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

C9399

Unclassified drugs or biologicals (Hospital Outpatient Use ONLY)

J8999

Prescription drug, oral, chemotherapeutic, Not Otherwise Specified

ICD-10 Diagnosis Codes That Support Medical Necessity

C33

Malignant neoplasm of trachea

C34.0

Malignant neoplasm of main bronchus

C34.00

Malignant neoplasm of unspecified main bronchus

C34.01

Malignant neoplasm of right main bronchus

C34.02

Malignant neoplasm of left main bronchus

C34.1

Malignant neoplasm of upper lobe, bronchus or lung

C34.10

Malignant neoplasm of upper lobe, unspecified bronchus or lung

C34.11

Malignant neoplasm of upper lobe, right bronchus or lung

C34.12

Malignant neoplasm of upper lobe, left bronchus or lung

C34.2

Malignant neoplasm of middle lobe, bronchus or lung

C34.3

Malignant neoplasm of lower lobe, bronchus or lung

C34.30

Malignant neoplasm of lower lobe, unspecified bronchus or lung

C34.31

Malignant neoplasm of lower lobe, right bronchus or lung

C34.32

Malignant neoplasm of lower lobe, left bronchus or lung

C34.8

Malignant neoplasm of overlapping sites of bronchus and lung

C34.80

Malignant neoplasm of overlapping sites of unspecified bronchus and lung

C34.81

Malignant neoplasm of overlapping sites of right bronchus and lung

C34.82

Malignant neoplasm of overlapping sites of left bronchus and lung

C34.9

Malignant neoplasm of unspecified part of bronchus or lung

C34.90

Malignant neoplasm of unspecified part of unspecified bronchus or lung

C34.91

Malignant neoplasm of unspecified part of right bronchus or lung

C34.92

Malignant neoplasm of unspecified part of left bronchus or lung

C49.4 – C49.5

Malignant neoplasm of connective and soft tissue of abdomen or pelvis

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: 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:

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

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 8/28/17]. Available from: http://www.clinicalpharmacology.com/.
  2. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 8/28/17]. Available from: http://clinicaltrials.gov/.
  3. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 8/28/17]. Available from: http://www.thomsonhc.com/.
  4. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Non-small cell lung cancer, v. 8.2017 [cited 8/28/17]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  5. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Soft tissue sarcoma, v. 2.2017 [cited 8/28/17]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  6. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2017 [cited 8/28/17]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  7. Novartis. Zykadia (ceritinib) capsule. 2017 [cited 8/28/17]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fff5d805-4ffd-4e8e-8e63-6f129697563e/.
  8. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 8/28/17]. 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 09/13/17.

GUIDELINE UPDATE INFORMATION:

09/15/14

New Medical Coverage Guideline.

11/01/15

Revision: ICD-9 Codes deleted.

01/15/16

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

09/15/16

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

10/01/16

Revision to guideline; consisting of updating ICD10 codes.

07/15/17

Revision to guideline; updated position statement with new NCCN recommendations.

10/15/17

Review and revision to guideline, consisting of updating position statement, coding, references.

Date Printed: October 17, 2017: 04:16 PM