Medical Drug Criteria (MDC)

Policy Num:       M3.001.002
Policy Name:     Radio 223 Injection (Xofijo)
Policy ID:           [M3.001.002]  [Ac / MA / M+ / P+]  [0.00.00]

Last Review:      May 06, 2025
Next Review:      May 20, 2026

Related Policies: A54559

Radio 223 Injection (Xofijo)

Summary

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".

objective

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.

Policy Statements

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 5

0 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.

Preauthorization required:

Prostate cancer individual:

• Resistant to castration, AND
• has symptomatic bone metastases, AND
• no known visceral metastatic disease, AND
• not receiving cytotoxic chemotherapeutic drugs

Policy Guidelines

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

BACKGROUD

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.

dosage/administration

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 5

0 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.

References

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/.

2. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; 2014 [cited 2014 Jan 24]. In: STAT! Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.

3. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2014 [cited 2014 Jan 24]. Available from: http://www.clinicalpharmacology.com/.

4. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2014 Jan 24]. Available from: http://www.thomsonhc.com/.

5. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2014 [cited 2014 Jan 24]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.

6. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2014 Jan 24]. Available from: http://clinicaltrials.gov/.

7. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2014 [cited 2014 Jan 24]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.

8. Prostate cancer treatment guidelines for patients [Internet]. Version 1.2014. Fort Washington (PA): National Comprehensive Cancer Network; 2014 [cited 2014 Jan 24]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.

9. NCCN Guidelines, Version3, 2016 Prostate Cancer

10. Bone metastases in advance prostate cancer: Management – Up to Date (20216)

11. DrugDex 2016

Codes

Policy History