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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-J1000-36

Original Effective Date: 09/15/11

Reviewed: 03/08/17

Revised: 07/01/17

Subject: Abiraterone Acetate (Zytiga®) 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.

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

Updates

 
           

DESCRIPTION:

Prostate cancer remains the most common non-cutaneous malignancy among men worldwide. Prostate cancer is a complex disease, with many controversial aspects of management. Prostate cancer is an androgen dependent disease that initially responds but later becomes resistant to established therapies that reduce circulating testosterone levels or inhibit androgen binding to androgen receptor (AR). Reactivation of the disease despite castrate levels of testosterone (<50 ng/dL) represents a transition to the lethal phenotype of castration-resistant prostate cancer (CRPC). This state is now recognized to be driven by AR signaling, in part due to overexpression of the androgen receptor itself.

Abiraterone (Zytiga) is a small molecule inhibitor of 17 alpha-monooxygenase, which is a member of the cytochrome P450 family that catalyzes the 17 alpha-hydroxylation of intermediates of steroid biosynthesis involved in testosterone synthesis. Abiraterone was initially approved by the FDA in April 2011 in combination with low-dose prednisone for the treatment of men with metastatic CRPC who have received prior chemotherapy containing docetaxel. This approved was based principally on the results of a phase III, randomized, placebo controlled trial (COU-AA-301, n=1195) in which subjects were randomized to receive either abiraterone 1,000 mg daily or placebo (both arms received concomitant prednisone). The study was unblinded after a pre-specified interim analysis demonstrated a statistically significant improvement in overall survival in subjects receiving abiraterone. The median survival was 15.8 months vs. 11.2 months in the abiraterone and placebo arm, respectively (HR 0.74; 95% CI 0.64 to 0.86, p<0.0001). In December 2012, the approval of abiraterone was expanded to include the treatment of men with metastatic CRPC as a first-line option (prior to other chemotherapy). The expanded approval is based on a phase III study of over 1,000 male subjects with late-stage CRPC who had not received prior chemotherapy and was designed to measure the length of overall and progression free survival. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (HR 0.53; 95% CI 0.45 to 0.62, p<0.001). In the extended final survival analysis over a median follow-up period of 49.2 months, overall survival was improved with abiraterone-prednisone (34.7 months) vs. 30.3 months for prednisone alone (HR 0.81; 95% CI 0.7 to 0.93, p=0.0033).

The National Comprehensive Cancer Network (NCCN) Prostate Cancer Guidelines (Version 1.2017) list abiraterone with prednisone as an option for initial therapy in the treatment of metastatic CRPC (without visceral metastases - category 1, with visceral metastases – category 2A). Abiraterone is a category 1 recommenation as second-line therapy following docetaxel (Taxotere®) therapy in persons with metastatic CRPC and category 2 following enzalutamide (Xtandi®) (both with or without visceral metastases). The NCCN recommends that patients whose disease progresses to CRPC during primary androgen deprivation therapy (ADT) should receive a laboratory assessment to assure a castrate level of testosterone (<50 ng/dL) has been achieved.

POSITION STATEMENT:

Initiation of abiraterone acetate (Zytiga) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with metastatic, castration-recurrent prostate cancer (CRPC, a.k.a., castration-resistant or hormone-refractory prostate cancer) – lab documentation of a recent (past 90 days) serum testosterone level at castrate level (<50 ng/dL) must be submitted for members receiving medical castration. A chart note documenting a bilateral orchiectomy must be submitted for members who have received surgical castration.

2. Abiraterone is used in combination with prednisone

3. The dosage does not exceed 1,000 mg (four 250 mg tablets or two 500 mg tablets) daily

4. Abiraterone is not used concomitantly with ANY of the following:

a) Cabazitaxel (Jevtana)

b) Docetaxel (Taxotere)

c) Enzalutamide (Xtandi)

d) Mitoxantrone (Novantrone)

e) Radium-223 (Xofigo)

f) Sipuleucel-T (Provenge)

Approval duration: 12 months

Continuation of abiraterone acetate (Zytiga) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member has demonstrated a beneficial clinical response to therapy

2. The member has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of metastatic prostate cancer, OR the member has previously met ALL indication-specific criteria

3. Abiraterone is not used concomitantly with ANY of the following:

a) Cabazitaxel (Jevtana)

b) Docetaxel (Taxotere)

c) Enzalutamide (Xtandi)

d) Mitoxantrone (Novantrone)

e) Radium-223 (Xofigo)

f) Sipuleucel-T (Provenge®)

4. The dosage does not exceed 1,000 mg (four 250 mg tablets or two 500 mg tablets) daily

Approval duration: 12 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: abiraterone is indicated for use in combination with prednisone for the treatment of persons with metastatic castration-resistant prostate cancer. Although initially approved for use following chemotherapy, the indication was expanded in December 2012 to include treatment prior to treatment with chemotherapy. Abiraterone should be administered as a 1,000 mg dose (two 500 mg or four 250 mg tablets) once daily in combination with prednisone 5 mg twice daily. Additionally, it should always be taken on an empty stomach to prevent supratherapeutic concentrations. The package insert advises against eating 2 hours before or 1 hour after administration. The tablets should be swallowed whole; do not crust or chew tablets.

Dose Adjustments

Baseline moderate hepatic impairment: The initial dose for members with moderate hepatic impairment (Child-Pugh class B) should be reduced to 250 mg once daily. Do NOT use in patients with severe baseline hepatic impairment (Child-Pugh Class C). Monitor ALT, AST and bilirubin prior to therapy initiation, every week for 1 month, every 2 weeks for the following 2 months and monthly thereafter; if elevation in ALT and/or AST exceed 5 times the upper limit of normal (ULN) or total bilirubin exceeds 3 times the ULN, discontinue therapy and do not reinitiate.

Hepatotoxicity: For members with normal hepatic function who develop hepatotoxicity while on therapy:

o First elevation: ALT and/or AST greater than 5 times ULN or total bilirubin 3 times ULN interrupt therapy and reinitiate at 750 mg daily once members levels return to baseline or less than or equal to 2.5 times the ULN for ALT and/or AST or 1.5 times ULN for bilirubin. Monitor ALT, AST and bilirubin at a minimum of every two weeks for three months and monthly thereafter

o Recurrence after reduction to 750 mg: reinitiate at 500 mg once daily once members LFTs to baseline or less than or equal to 2.5 times the ULN for ALT and/or AST or 1.5 times ULN for bilirubin

o Recurrence after reduction to 500 mg: discontinue therapy

o Permanently discontinue for patients who develop a concurrent elevation of ALT greater than 3 times ULN and total bilirubin greater than 2 times ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation.

Strong CYP3A4 Inducers: Avoid concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during treatment if possible. Although there are no clinical data with this dose adjustment, because of the potential for an interaction, if a strong CYP3A4 inducer MUST be co-administered, increase the dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day). Reduce the dose back to the previous dose and frequency, if the concomitant strong CYP3A4 inducer is discontinued.

Drug Availability: abiraterone is supplied as 250 mg and 500 mg tablets.

PRECAUTIONS:

CONTRAINDICATIONS

Abiraterone is contraindicated in women who are or may become pregnant.

WARNINGS

Mineralocorticoid excess: Use abiraterone with caution in members with a history of cardiovascular disease. The safety of abiraterone in members with a LVEF less than 50% or NYHA Class III or IV heart failure has not been established. Control hypertension and correct hypokalemia prior to treatment initiation. Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly.

Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations.

Hepatotoxicity: Increases in liver enzymes have led to drug interruption, dose modification and/or discontinuation. Monitor liver function and modify, interrupt, or discontinue abiraterone dosing as recommended.

Food effect - Abiraterone must be taken on an empty stomach. Exposure may increase up to 10-fold when abiraterone is taken with meals.

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

C61

Malignant neoplasm of prostate

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

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

DEFINITIONS:

Castrate-resistant/recurrent prostate cancer (CRPC): disease progression despite androgen deprivation therapy (ADT) with either medication or surgery (i.e., removal/destruction of testicles, and may present as either a continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases.

Metastatic cancer: when cancer spreads from the primary site (place where it started) to other places in the body.

RELATED GUIDELINES:

Cabazitaxel (Jevtana®), 09-J1000-77
Cryosurgical Ablation of the Prostate (CSAP), 02-54000-14

Docetaxel (Taxotere®) IV, 09-J0000-95

Enzalutamide (Xtandi), 09-J1000-85

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

Radium Ra 223 (Xofigo®) Injection, 09-J2000-01

Sipuleucel-T (Provenge®), 09-J1000-29

OTHER:

None

REFERENCES:

  1. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005.
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. Available at: www.clinicalpharmacilogy-ip.com. Accessed 2/15/16.
  3. Dayyani F, Gallick GE, Logothetis CJ et al. Novel therapies for metastatic castrate-resistant prostate cancer. J Natl Cancer Inst 2011;103:1665-75.
  4. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012 Oct;13(10):983-92. Epub 2012 Sep 18.
  5. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 2/17/17.
  6. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 2/21/17.
  7. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Prostate Cancer. Version1.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf. Accessed 2/21/17.
  8. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017 Feb 17]. Available from:http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  9. Sartor AO, Fitzpatrick JM. Urologists and oncologists: adapting to a new treatment paradigm in castration-resistant prostate cancer (CRPC).BJU Int 2012;110:328-335.
  10. Zytiga (abiraterone acetate) [package insert]. Janssen Biotech, Inc. Horsham (PA): April 2017.
  11. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138-48. Epub 2012 Dec 10.
  12. Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015 Feb;16(2):152-60. Epub 2015 Jan 16.

COMMITTEE APPROVAL:

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

GUIDELINE UPDATE INFORMATION:

09/15/11

New Pharmacy Coverage Guideline.

11/15/11

Revision to guideline; consisting of removing 18 years of age requirement for coverage.

09/15/12

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

02/15/13

Revision to guideline; consisting of adding additional indication to position statement, revising and reformatting description, dosage/administration, precautions section; adding definition and related guidelines; updating references.

04/15/13

Review and revision to guideline; consisting of revising position statement to include approval duration; updating description section and references.

04/15/14

Review and revision to guideline; consisting of reformatting position statement, updating description section, references and program exceptions.

04/15/15

Review and revision to guideline; consisting of description section, position statement to include continuation criteria, dosage/administration, definitions, and references.

04/15/16

Review and revision to guideline consisting of description section, position statement, definitions, and references.

04/15/17

Review and revision to guideline consisting of description section, position statement, precautions section, and references.

07/01/17

Revision to guideline consisting of updating the position statement and dosage/administration section as a result of a new 500 mg tablet strength.

Date Printed: October 20, 2017: 08:41 AM