Print

Date Printed: August 23, 2017: 01:33 PM

Private Property of Blue Cross and Blue Shield of Florida.
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: 08/10/16

Revised: 07/15/17

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 4.2016) recommend ceritinib as second-line therapy as a single agent for ALK-positive recurrent or metastatic disease for intolerance to crizotinib, asymptomatic disease with rapid radiologic progression or threatened organ function on crizotinib, or progression on crizotinib.

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 as detected by an FDA-approved test – laboratory documentation must be provided

c. Ceritinib will be used as monotherapy

d. The 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 as detected by an FDA-approved test

b. Ceritinib will be used as monotherapy

c. The 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, OR the member has previously met all indication-specific initiation criteria
  2. Ceritinib is used as monotherapy
  3. Member’s disease has not progressed during treatment with ceritinib
  4. The 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

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

Drug-induced hepatotoxicity

• ALT or AST greater than 5 times ULN with total bilirubin less than or equal to 2 times ULN: Withhold until recovery, then resume with a 150 mg dose reduction

• ALT or AST greater than 3 times ULN with total bilirubin less than or equal to 2 times ULN: Discontinue

Safety and tolerability

• Dosing reductions of 150 mg or discontinuation of drug may be required based on individual safety and tolerability

Drug Availability

150 mg capsule

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 Diagnoses Codes That Support Medical Necessity

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

C49.A0 – C49.A9

Gastrointestinal stromal tumor

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.; 2016 [cited 2016 Jul 16]. Available from: http://www.clinicalpharmacology.com/.
  2. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2016 Jul 16]. Available from: http://clinicaltrials.gov/.
  3. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2016 Jul 16]. 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. 4.2016 [cited 2016 Jul 16]. 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. 1.2015 [cited 2016 Jule 16]. 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; 2015 [cited 2016 Jul 16]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  7. Novartis. Zykadia (ceritinib) capsule. 2014 [cited 2016 Jul 16]. 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; 2016 [cited 2016 Jul 16]. 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 08/10/16.

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.

Date Printed: August 23, 2017: 01:33 PM