Medical PolicyMedical Policy
Policy Num: 08.001.038
Policy Name: Radio 223 Injection (Xofigo)
Policy ID: [08.001.038] [Ac / L / M+ / P+] [0.00.00]
Last Review: November 10, 2021
Next Review: Policy Archived
Issue: 11:2021
ARCHIVED
Related Policies BCBS: None
Related Policies TSSS: None
| Population Reference No. | Populations | Interventions | Comparators | Outcomes |
| 1 | Individuals: · With castrate resistant, androgen deprived painful bone metastatic prostate cancer | Interventions of interest are: · Treatment with radium 223 injection(Xofigo) | Comparators of interest are: · Standard management | Relevant outcomes include: · Adverse effects · Overall morbidity and mortality · Quality of life |
Approximately 240,000 men in the United States are expected to be diagnosed with prostate cancer in 2016. Although most are diagnosed at an early localized stage, up to 30% of cases will be repeated after surgical therapy or curative radiotherapy.
Androgen deprivation therapy, either with surgical or gonadotropin releasing castration analogous to the hormone, is normally initiated to control the disease in people who have developed metastases. Unfortunately, almost all these cases will continue progressing. When patients turn to androgen deprivation therapy in the adjustment of "castration" levels of testosterone, patients receive the name of "castration-resistant".
The objective of this review is to demonstrate the safety and efficacy of radium 223 in patients with prostate cancer resistant to castration and symptomatic bone metastasis.
The radium 223 injection (Xofigo) is considered for payment when all of the following criteria for prostate cancer are fulfilled:
1. Insured is diagnosed metastatic prostate cancer resistant to castration.
2. Insured has symptomatic bone metastases.
3. Insured does not have any known visceral metastatic disease.
4. Radium 223 is not used concomitantly with cytotoxic chemotherapeutic drugs (for example, docetaxel, cabazitaxel, mitoxantrone).
5. The dosage does not exceed 1 injection every 28 days during 6 injections.
Note. The therapy of androgens deprivation (for example, leuprolide, degarelix, abiraterone), denosumab, or zoledronic acid are not considered cytotoxic chemotherapy. The concomitant use is permitted.
Duration of approval: 6 months
50 kbq (1.35 microcurie) per kg of body weight administered at intervals of 4 weeks of 6 injections. Refer to the product label for factors table of decay correction.
Calculate administration volume using patient weight, radioactivity content (at the reference date), and decay correction factor; determine net patient dose immediately before and after administration with an appropriate radioisotope dose calibrator; refer to product labeling for further details. Prior to initial dose, ANC should be ≥1,500/mm3, platelets ≥100,000/mm3, and hemoglobin ≥10 g/dL
BlueCard/National Account Issues
N/A
The current therapeutic options for metastatic prostate cancer resistant to castration include both the systemic and bone-directed treatments. While the systemic therapies (for example, abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, sipuleucel-T) are not directed to a specific organ, bone oriented therapies are active predominantly in the marrow and do not treat the lymph nodes and the visceral metastasis.
Available agents include the zoledronic acid (Zometa), denosumab (Xgeva), and the strontium 89 radioisotopes (Metastron) and the samarium 153 (Quadramet) - none of which has shown that possesses an advantage of survival, (zoledronic acid and denosumab were approved to delay the time in skeletal related events; radioisotopes were approved for the alleviation of the bone pain).
Radium 223 (Xofigo), is an alpha emitting radiopharmaceutical, approved by the Food and Drug Administration (FDA) on May 15, 2013 for the treatment of patients with prostate cancer resistant to castration with symptomatic bone metastases and without evidence of visceral metastatic disease.
Radium 223 imitates calcium and forms complexes with hydroxyapatite in areas of increased bone turnover. This gives rise to a high frequency of double-stranded DNA breaks in adjacent cells and results in an anti-tumor effect in bone metastases, and ultimately, the prolonged survival of patients. While the radio 223 is not intended to be used in combination with chemotherapy, due to the additive possibility of myelosuppression, the concomitant use of denosumab or zoledronic acid does not interfere with the beneficial effects.
The safety and efficacy of radium 223 were evaluated in patients with prostate cancer resistant to castration and symptomatic bone metastases in a double-blind study, randomized, and controlled with phase III placebo. Individuals with visceral metastatic disease were excluded from the study. The subjects were randomized 2:1 to receive radium 223 (dosage: 50 kBq / kg IV) every 28 days during six injections plus the best support treatment. The primary assessment criterion was overall survival with a predefined intermediate analysis; a secondary objective was the effect on symptomatic skeletal events.
In the predefined interim analysis, the primary endpoint of overall survival met the limit of statistical significance, revealing a decreased risk of death within 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 radio 223 (n = 809 patients) compared to 11.2 months in the placebo group (n = 268 patients). The time of symptomatic skeletal events also delayed in the radius of the arm 223 with a hazard ratio of 0.610 (95% CI: 0.461, 0.807, p = 0.00046).
In the predefined intermediate analysis, the main variable of global survival met the limit of statistics significance, that reveals a decrease in the risk of death in the radio 223 group with a "hazard ratio" of 0.695 (IC of 95%: 0.522, 0.875, p = 0.00185). Median overall survival was 14 months in the 223-radium group (n = 809 patients) in comparison with 11.2 months in the placebo group (n = 268 patients). Time of symptomatic skeletal events was also delayed in the radium of arm 223 with a hazard ratio of 0.610 (95% CI: 0.461, 0.807, p = 0.00046).
The average time of symptomatic bone events was of 13.5 months in comparison with 8.4 months for the radium 223 and placebo, respectively. The most common adverse reactions (> 10%) in patients who received radium 223 were nausea, diarrhea, vomiting and peripheral edema. The most common hematologic laboratory abnormalities (> 10%) were anemia, lymphopenia, leukopenia, thrombocytopenia, and neutropenia.
Guidelines from the National Comprehensive Cancer Network (NCCN) for prostate cancer (Version 1.2014) designates the radium 223, as first or second line of therapeutic option for the symptomatic bone metastasis (category 1) for prostate cancer resistant to castration.
The purpose of this rationale is to review the radiopharmaceutical properties, dosing, safety and adverse effects of Radium 223.
Population Reference No. 1
With castrate resistant, androgen deprived painful bone metastatic prostate cancer.
NDIVIDUALS with castrate resistant, androgen deprived painful bone metastatic prostate cancer
| Population Reference No. 1 Policy Statement | [X] MedicallyNecessary | [ ] Investigational | [ ] Not Medically Necessary |
N/A
N/A
N/A
1. Bayer HealthCare Pharmaceuticals, Inc. Xofigo (radium ra 223 dichloride) injection. 2014 [cited 2014 Jan 24]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a398400e-bd31-41a9-9696- 4f7c06569ede/.
3. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2014 [cited 2014 Jan 24]. Available from: http://www.clinicalpharmacology.com/.
| Codes | Number | Description |
| HCPCS | A9606 | Radium RA-223 dichloride, therapeutic, per microcurie |
| ICD-10-CM | C61 | Malignant neoplasm of prostate |
| | C79.51 | Secondary malignant neoplasm of bone |
Some modifiers
| Date | Action | Description |
| 11/10/21 | Annual review, Archived policy | Reviewed by the Providers Advisory Committee. Archived policy. No changes in policy statement. |
| 11/11/20 | Annual review | Reviewed by the Providers Advisory Committee. No changes in policy statement. |
| 11/14/19 | Annual review | Reviewed by the Providers Advisory Committee. No changes on policy statement. |
| 11/14/18 | Annual review | Reviewed by the Providers Advisory Committee. No changes on policy. |
| 09/25/18 | | |
| 12/29/17 | | |
| 10/28/16 | | |
| 05/08/15 | | |
| 08/05/14 | Created | New Policy |