Print

Date Printed: October 17, 2017: 04:27 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-J2000-01

Original Effective Date: 09/15/13

Reviewed: 03/08/17

Revised: 04/15/17

Subject: Radium Ra 223 (Xofigo®) Injection

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 is a leading cause of non-cutaneous cancer in men. Although most will be diagnosed at an early localized stage, up to 30% of cases will recur following curative surgical or radiation therapy. Androgen deprivation therapy with either surgical castration or gonadotropin releasing hormone (GnRH) analogs is commonly initiated to control disease in those who have developed metastases. Unfortunately, nearly all of these cases will continue to progress; when patients recur on androgen deprivation therapy in the setting of “castrate” levels of testosterone, patients are termed “castration-resistant” or “castration-recurrent”. Current treatment options for metastatic castration-resistant/recurrent prostate cancer (CRPC) include both systemic and bone-targeted therapies. While systemic therapies (e.g., abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, sipuleucel-T) are not targeted to a specific organ, bone-targeted therapies are active predominately in the bone and leave lymph node and visceral metastases untreated. Available agents include zoledronic acid (Zometa®), denosumab (Xgeva®), and the radioisotopes strontium 89 (Metastron®) and samarium 153 (Quadramet®) – none of which have been shown to possess a survival advantage (zoledronic acid and denosumab were approved based on a delay in time to skeletal related events; radioisotopes were approved for palliation of bone pain).

Radium 223 (Xofigo®), an alpha emitting radiopharmaceutical, was approved by the U.S. Food and Drug Administration (FDA) on May 15, 2013 for the treatment of CRPC patients with symptomatic bone metastases and no evidence of visceral metastatic disease. Radium 223 mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover; this leads to a high frequency of double-strand DNA breaks in adjacent cells and results in an anti-tumor effect on bone metastases and ultimately extended patient survival. While radium 223 is not intended to be used in combination with chemotherapy due to the potential for additive myelosuppression, concomitant use of denosumab or zoledronic acid does not interfere with any beneficial effects.

The safety and efficacy of radium 223 were evaluated in subjects with CRPC and symptomatic bone metastases in a randomized, double-blind, placebo-controlled Phase III study. Individuals with visceral metastatic disease were excluded from the study. Subjects were randomized 2:1 to receive radium 223 (dose: 50 kBq/kg IV) every 28 days for six injections plus best supportive care or placebo plus best supportive care. The primary endpoint was overall survival with one predefined interim analysis; a secondary endpoint was time to symptomatic skeletal events. At the predefined interim analysis, the primary endpoint of overall survival met the boundary for statistical significance revealing a decrease in the risk of death in the radium 223 group with a hazard ratio of 0.695 (95% CI: 0.522, 0.875; p=0.00185). The median overall survival was 14 months in the radium 223 group (n=809 patients) compared to 11.2 months in the placebo group (n=268 patients). The time to symptomatic skeletal events was also delayed in the radium 223 arm with a hazard ratio of 0.610 (95% CI: 0.461, 0.807; p=0.00046). The median time to symptomatic skeletal events was 13.5 months compared with 8.4 months for radium 223 and placebo, respectively. The most common adverse reactions (>10%) in patients receiving radium 223 were nausea, diarrhea, vomiting and, peripheral edema. The most common hematologic laboratory abnormalities (> 10%) were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.

The National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer (Version 1.2017) designate radium 223 as a category 1 first-line or second-line (i.e., after failure of enzalutamide, abiraterone, or docetaxel) therapeutic option for symptomatic bone metastases in patients with CRPC without visceral metastases. The NCCN states that radium 223 alone has not been shown to extend survival in men with visceral metastases or bulky lymph node metastases (>3 to 4 cm) and is not recommended in this setting. 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:

Radium Ra 223 (Xofigo®) injection meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed of 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. Member has symptomatic bone metastases

3. Member does not have any known visceral metastatic disease (e.g., brain, liver, lung) or bulky lymph node metastases (>3 to 4 cm)

4. Radium 223 is not used concomitantly with any cytotoxic chemotherapy agents (e.g., docetaxel, cabazitaxel, mitoxantrone), AND/OR with either abiraterone (Zytiga®) or enzalutamide (Xtandi®).

NOTE: Androgen deprivation therapy (e.g., leuprolide, degarelix), denosumab, or zoledronic acid are not considered cytotoxic chemotherapy; concomitant use is permitted.

5. The dosage does not exceed 1 injection of 55 kBq/kg (1.49 microcurie) every 28 days for 6 total injections

6. The member has not previously received treatment with radium 223

Duration of approval: 6 months (to allow for a total of 6 injections)

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

Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. The dose regimen is 55 kBq (1.49 microcurie) per kg body weight, given at 4 week intervals for 6 injections. Immediately before and after administration, the net patient dose of administered Xofigo should be determined by measurement in an appropriate radioisotope dose calibrator that has been calibrated with a National Institute of Standards and Technology (NIST) traceable radium-223 standard (available upon request from Bayer) and corrected for decay using the date and time of calibration. Reference the product label for the decay correction factor table.

Dose Adjustments

None

Drug Availability

Single-use vial at a concentration of 1,100 kBq/mL (30 microcurie/mL) at the reference date with a total radioactivity of 6,600 kBq/vial (178 microcurie/vial) at the reference date

PRECAUTIONS:

Contraindications

Pregnancy

Precautions/Warnings

Bone Marrow Suppression: Measure blood counts prior to treatment initiation and before every dose of Xofigo. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after treatment.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

A9606

Radium ra-223 dichloride, therapeutic, per microcurie

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

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.

RELATED GUIDELINES:

Abiraterone acetate (Zytiga®), 09-J1000-36
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

Sipuleucel-T (Provenge®), 09-J1000-29

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017 Feb 17]. Available from: http://www.clinicalpharmacology.com/.
  2. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017 Feb 17]. Available from: http://www.thomsonhc.com/.
  3. Hoskin P, Sartor O, O'Sullivan JM, et al. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol. 2014 Nov;15(12):1397-406. Epub 2014 Oct 17.
  4. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 2/20/17.
  5. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 1.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf. Accessed 02/20/2017.
  6. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 201 [cited 2017 Feb 17]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  7. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013 Jul 18;369(3):213-23.
  8. Sartor O, Coleman R, Nilsson S, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014 Jun;15(7):738-46. Epub 2014 May 13.
  9. Xofigo (radium chloride ra-223) [package insert]. Bayer HealthCare. Wayne (NJ): March 2016.

COMMITTEE APPROVAL:

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

GUIDELINE UPDATE INFORMATION:

09/15/13

New Medical Coverage Guideline.

04/15/14

Review and revision to guideline; consisting of description, position statement, decision tree, references

04/15/15

Review and revision to guideline; consisting of description, dosage/administration, HCPCS coding, and references.

11/01/15

Revision: ICD-9 Codes deleted.

04/15/16

Review and revision to guideline consisting of description section, dosage/administration, definitions, and references.

09/15/16

Revision to guideline consisting of position statement, dosage/administration, and references.

11/15/16

Revision to guideline consisting of updating position statement to allow 6 total doses during a 6 month approval period

04/15/17

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

Date Printed: October 17, 2017: 04:27 PM