Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Radium Ra 223 dichloride (XofigoŽ) Injection (Independence Administrators)

Policy #:08.01.14e

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.


This policy only applies to members for whom Independence Administrators serves as the claims administrator. For all other Independence members, refer to the policy entitled Radiation Therapy Services.


MEDICALLY NECESSARY

Radium Ra 223 dichloride (XofigoŽ) injection is considered medically necessary and, therefore, covered for a maximum of six injections for the treatment of castration resistant prostate cancer (also known as hormone resistant prostate cancer) when all of the following criteria are met:
  • The individual has castration (hormone) resistant prostate cancer, as defined by:
    • A serum testosterone level of less than < 50 ng/dL and either
      1. Sequential rise of prostate specific antigen (PSA) levels or
      2. Worsening of existing bone metastases or development of new bone metastases on a bone scan performed within the past 60 days despite androgen-deprivation treatment
    • Documented failure of available hormonal therapies. The individual may be kept on their ablative hormonal treatment to maintain castrate levels of serum testosterone.
  • The individual has symptomatic skeletal (bone) metastases
  • The individual has no evidence of visceral metastases or bulky regional lymph nodes > 3 cm on imaging performed within the past 30 days

EXPERIMENTAL/INVESTIGATIONAL

All other uses for radium Ra 223 dichloride (XofigoŽ) injection, including the use of more than six injections, are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

BILLING REQUIREMENTS

Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

If there is no specific HCPCS code available for the drug administered, then the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).
Guidelines

The US Food and Drug Administration (FDA) has approved radium Ra 223 dichloride (XofigoŽ) injection in individuals who have castration-resistant prostate cancer (defined as having a testosterone level of less than 50 ng/dL).

LABORATORY VALUES

According to the FDA-approved label, the individual should have an absolute neutrophil count (ANC) of
1.5X109/L or greater, platelet count of 100X109/L or greater, and a hemoglobin of 10g/dL or greater prior to initial dose. Prior to subsequent doses, the individual should have an ANC of 1X109/L or greater and a platelet count of 50X109/L or greater. If within 6 to 8 weeks after the last administration of radium Ra 223 dichloride (XofigoŽ) injection there is no recovery of the absolute neutrophil count (ANC), platelet count, and hemoglobin levels to the values listed above (despite receiving supportive care), further treatment with radium Ra 223 dichloride (XofigoŽ) injection should be discontinued.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The Eastern Cooperative Oncology Group (ECOG), established in 1955, was one of the first groups to coordinate multicenter cancer clinical trials. The National Cancer Institute (NCI) is the primary funding source, and ECOG has evolved from a small consortium of institutions in the eastern United States to one of the largest clinical cancer research organizations in the country. As part of their work in the treatment of cancer, ECOG has developed the ECOG Performance Status (EPS), originally published in 1982 in the American Journal of Clinical Oncology. The use of the scales and the criteria in the EPS allows clinicians and researchers to determine an individual’s disease progression in terms of how the activities of daily living (ADL) are affected.

ECOG Performance Status
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work, office work)
2
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3
Capable of only limited self care, confined to bed or chair more than 50 percent of waking hours
4
Completely disabled. Cannot carry on any self care: Totally confined to bed or chair
5
Dead
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, radium Ra 223 dichloride (XofigoŽ) injection is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Radium Ra 223 dichloride (XofigoŽ) injection was approved by the FDA on May 15, 2013 for the treatment of individuals with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease.

Description

Prostate cancer is the second leading cause of cancer-related deaths among American men, with an estimated incidence of 233,00 new cases and 29,480 deaths estimated for 2014. The widespread use of the prostate-specific antigen (PSA) test for the screening and monitoring of individuals with prostate cancer has allowed for the majority of prostate cancer cases to be diagnosed at a localized stage. Despite early detection and appropriate treatment, some individuals progress to metastatic, hormone-refractory prostate cancer (mHRPC) after the failure of several lines of antihormonal therapies; furthermore, more than 90% of these individuals have radiologic evidence of bone metastases, which are a major cause of death, disability, decreased quality of life, and increased treatment cost among these individuals. Unlike deaths from many other types of cancer, deaths from prostate cancer are often due to bone disease and its complications. Weakened bones due to cancer metastases can lead to fractures and compression of the spinal cord. They necessitate procedures such as surgery and radiation, which are designed to prevent or manage bone complications. The primary goal of treatment for bone metastases is to prevent the occurrence of debilitating bone complications that can affect an individual's quality of life.

Radium Ra 223 dichloride (XofigoŽ) injection is the first alpha particle-emitting radioactive therapeutic agent approved by the US Food and Drug Administration (FDA), on May 15, 2013, for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease.

Radium Ra 223 dichloride (XofigoŽ) injection mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover. The high-energy alpha particle radiation causes breaks in the double-stranded DNA of the targeted area, resulting in an anti-tumor effect on the bone metastases. The short path of the alpha particles limits the damage to the surrounding normal tissue and bone marrow.

The dosing regimen of radium Ra 223 dichloride (XofigoŽ) injection is 50 kBq (1.35 microcurie) per kg body weight, given at 4-week intervals for a total of 6 injections. It is administered by a slow intravenous injection over 1 minute. Toxicities resulting from this therapy include a low risk of bone marrow suppression, gastrointestinal symptoms, and the possibility of impaired fertility.

PEER-REVIEWED LITERATURE

SUMMARY
The FDA granted approval of radium Ra 223 dichloride (XofigoŽ) injection based on a Phase III, double-blind, randomized, placebo-controlled clinical trial. The ALSYMPCA (ALpharadin in SYMptomatic Prostate Cancer) trial included individuals with castration-resistant prostate cancer who had two or more bone metastases that were symptomatic. In addition, these individuals had received, were not eligible to receive, or declined therapy with, docetaxel. Eighty-six percent of individuals had an Eastern Cooperative Oncology Group (ECOG) performance status of zero to one. Individuals were excluded from the study if they experienced visceral metastases and malignant lymphadenopathy exceeding 3 cm.

A total of 809 individuals were randomized 2:1 to receive radium Ra 223 dichloride (XofigoŽ) injection 50 kBq (1.35 microcurie)/kg intravenously every 4 weeks for 6 cycles (n=541) plus best standard of care or matching placebo plus best standard of care (n=268). (Best standard of care included local external beam radiation therapy [EBRT], corticosteroids, antiandrogens, estrogens, estramustine, or ketoconazole.)

Individuals receiving radium Ra 223 dichloride (XofigoŽ) injection plus best standard of care experienced a statistically significant increase in median overall survival (14.9 months) when compared to individuals receiving placebo plus best standard of care (11.3 months). A key secondary outcome reported a statistically significant prolonged median time to first symptomatic skeletal event (SSE) for individuals receiving radium Ra 223 dichloride (XofigoŽ) injection plus best standard of care (15.6 months) when compared to individuals receiving placebo plus best standard of care (9.8 months).

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


Cookson MS, Lowrance WT, Murad MH, Kibel AS; American Urological Association. Castration-resistant prostate cancer: AUA guideline amendment. J Urol. 2015;193(2):491-9.

Cookson MS, Roth BJ, Dahm P, et al. Castration-resistant prostate cancer: AUA Guideline. J Urol. 2013;190(2):429-38.

Dawson NA. Overview of the treatment of disseminated castration-sensitive prostate cancer. July 7, 2017. Available at: http://www.uptodate.com/contents/overview-of-the-treatment-of-disseminated-prostate-cancer?detectedLanguage=en&source=search_result&search=xofigo&selectedTitle=5%7E10&provider=noProvider#H95566246 [via subscription only]. Accessed November 12, 2018.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Radium-223 Dichloride. [ClinicalKey Web site]. 08/01/2017. Available at: https://www.clinicalkey.com/. [via subscription only]. Accessed November 12, 2018.

Lowrance WT, Roth BJ, Kirkby E, et al. Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015. J Urol. 2016;195(5):1444-52.

Micromedex Solutions. Radium Ra 223 Dichloride. 11/29/2016. [MicromedexŽ Solutions Web site]. Available at:http://www.micromedexsolutions.com/micromedex2/librarian/ [via subscription only]. Accessed November 12, 2018.

National Cancer Institute (NCI). Prostate Cancer Treatment (PDQ) - Health Professional Version. 10/12/2018. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/prostate/HealthProfessional/page1#Section_1679. Accessed November 12, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Prostate Cancer. Version 4.2018. 08/15/2018. [NCCN Web site]. Available at: http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf [via free subscription]. Accessed November 12, 2018.

Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213-23. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1213755. Accessed November 12, 2018.

Radium Ra 223 dichloride (XofigoŽ) Injection. Prescribing information. September 2018. Bayer HealthCare Pharmaceuticals, Inc. Whippany, NJ. Available at: http://www.xofigo-us.com/index.php. Accessed November 12, 2018.

Sartor AO, DiBiase SJ. Bone metastases in advanced prostate cancer: Management. June 12, 2018. Available at:http://www.uptodate.com/contents/management-of-bone-metastases-in-advanced-prostate-cancer?detectedLanguage=en&source=search_result&search=xofigo&selectedTitle=4%7E10&provider=noProvider [via subscription only]. Accessed November 12, 2018.

Terris MK. Metastatic and Advanced Prostate Cancer. July 19, 2018. Medscape Reference: Drugs, Diseases & Procedures. Available at: http://emedicine.medscape.com/article/454114-overview. Accessed November 12, 2018.

Thompson I, Thrasher JB, Aus G, Burnett AL, et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol. 2007;177(6):2106-31.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. XofigoŽ (radium Ra 223 dichloride) Injection NDA approval letter [FDA Web site]. 05/13/2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/203971Orig1s000ltr.pdf. Accessed November 12, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. XofigoŽ (radium Ra 223 dichloride) Injection drug label [FDA Web site]. 08/2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/203971s014lbl.pdf. Accessed November 12, 2018.

Vogelzang NJ, Helle SI, Johannessen DC, et al. Efficacy and safety of radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases who did or did not receive prior docetaxel (D) in the phase III ALSYMPCA trial. J Clin Oncol. 2013;31:Abstr 5068.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

C61 Malignant neoplasm of prostate

C79.51 Secondary malignant neoplasm of bone

C79.52 Secondary malignant neoplasm of bone marrow



HCPCS Level II Code Number(s)

A9606 Radium ra-223 dichloride, therapeutic, per microcurie


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions from 08.01.14e:
03/04/2019This version of the policy will become effective 03/04/2019.

The Medically Necessity criteria regarding the injection of Radium Ra 223 dichloride (XofigoŽ) for the treatment of castration resistant prostate cancer (also known as hormone resistant prostate cancer) have been revised.

Revisions from 08.01.14d:
11/08/2017The policy has been reviewed and reissued to communicate the Company’s continuing position on Radium Ra 223 dichloride (XofigoŽ) Injection.


Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date: 03/04/2019
Version Issued Date: 03/04/2019
Version Reissued Date: N/A

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Independence Blue Cross is an independent licensee of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.