Radiation Treatment with Azedra (Iobenguane I-131)
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
Azedra is a radioactive therapeutic agent indicated for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.
The efficacy of Azedra was established in Study IB12B, an open-label, single-arm, multicenter clinical trial. A total of 74 patients received the dosimetric dose of Azedra. Following dosimetry, 68 patients received at least one therapeutic dose and 50 patients received two therapeutic doses administered at least 90 days apart. The dosimetric dose was 185 mBq to 222 MBq (5 mCi to 6 mCi) for patients weighing > 50 kg and 3.7 MBq/kg (0.1 mCi/kg) for patients weighing ≤ 50 kg. The therapeutic dose was 18,500 MBq (500 mCi) for patients weighing > 62.5 kg and 296 MBq/kg (8 mCi/kg) for patients weighing ≤ 62.5 kg.
Primary outcome measure was the proportion of studied subjects with a reduction of all antihypertensive medications by at least 50% maintained for at least 6 months, which was observed in 25% of the patients (95% CI 16%, 37%). Key secondary outcome measure was the Proportion of subjects with overall tumor response of Complete Response or Partial Response by RECIST criteria, which was seen in 22% of the patients (95% CI 14%, 33%). Of these, 53% have sustained response of at least 6 months. Median overall survival was 37 months (95% CI 31, 49) from the time of first therapeutic dose. Median survival in patients who received one therapeutic dose and two therapeutic doses were 18 months and 44 months, respectively. The most common reason patients did not receive the second therapeutic dose of Azedra was due to myelosuppression that did not recover within the time according to protocol-specified criteria.
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
Azedra® is considered medically necessary for the treatment of an individual aged 12 years and older with iobenguane scan positivity who has inoperable locally advanced or metastatic pheochromocytoma or paraganglioma requiring systemic treatment.
II. Submission Requirements
A. Official pathology report documenting pheochromocytoma or paraganglioma.
B. Official radiology report of positive iobenguane scan.
C. In the absence of metastatic disease, a surgical or medical consult documenting the reason for inoperability.
A. Creatinine clearance < 30 mL/minute
B. Platelet count < 80,000
C. Absolute neutrophil count < 1,200/mcL
D. Liver dysfunction with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2.5 times the upper limit of normal or total bilirubin > 1.5 times the upper limit of normal
E. History of hepatitis or chronic alcohol abuse
F. History of external beam radiation to > 25% of the bone marrow
G. History of systemic radiotherapy resulting in myelosuppression within 3 months of proposed Azedra® administration.
IV. Precautions and Warnings
A. The official manufacturer’s prescribing information, precautions and radiation safety instructions packaged with the medication should be fully reviewed and understood before using Azedra®.
B. This radiopharmaceutical should be used by or under the supervision of physicians with specific training in the use of radiopharmaceuticals who have been authorized and approved by the appropriate governmental agency.
C. Concerns about the use of this radiopharmaceutical include but are not limited to:
1. Radiation safety in handling the preparation
2. Pregnancy, lactation and precautions for both women and men of reproductive potential on appropriate contraception methods including embryo-fetal toxicity and risks of infertility
3. Risk from radiation exposure
5. Leukemia and Secondary Myelodysplastic Syndrome
6. Renal toxicity including use with renal impairment
7. Hepatic toxicity including use with hepatic impairment
11. Pediatric and geriatric use.
A. Users should read the manufacturer’s insert for all specific instructions as they could change as more experience is gained in the patient population:
1. The current recommended dose of Azedra® is dependent on body weight. The drug is administered as a dosimetric dose followed by two therapeutic doses administered 90 days apart.
2. Users should familiarize themselves with the therapeutic dose adjustments that may be necessary based on the dosimetry results and reactions to treatment.
3. Particular attention should be given to the manufacturer’s instructions on the use of drugs that reduce catecholamine uptake or deplete catecholamine stores, mandatory thyroid blockade prior to treatment, as well as antiemetic and hydration requirements.
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this drug. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.
[INFORMATIONAL NOTE: Recently, the Food and Drug Administration (FDA) announced approval of Azedra® for adults and pediatric patients 12 years and older with iobenguane scan positivity who have inoperable locally advanced or metastatic pheochromocytoma or paraganglioma requiring systemic treatment. The approval is based on Study IB12B open-label, single arm multicenter trial (NCT00874614). The required dosimetric dose was administered to 74 patients. Sixty-eight (68) patients subsequently received at least one therapeutic dose. Of this group, 50 patients received two therapeutic doses 90 days apart. Thirty-five (35) of the 68 patients had prior surgery and systemic therapy (I-131 MIBG and/or chemotherapy) for pheochromocytoma or paraganglioma. Fifty percent (50%) had previous external beam radiation therapy. Lung and/or liver metastases were present at baseline in 32 of 64 evaluable patients. Sixty-one percent (61%) had bone metastases. The primary endpoint specified in the study was the proportion of patients with at least 50% reduction of all anti-hypertensive medications for a minimum of 6 months during the efficacy period of 1 year. Overall tumor response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). After one (1) year, patients entered four (4) additional years of planned follow-up. The primary endpoint was met by 25% (95% CI 16% to 37%) of those receiving one therapeutic dose and 32% (95% CI 21% to 46%) of patients who received two (2) therapeutic doses, achieving pre-specified success criteria. For objective tumor response, 23% of one dose and 30% of two dose patients’ populations achieved partial response (PR). The 12-month overall survival (OS) was 91% in one dose patients. Median OS was 36.7 months (95% CI 29.9 to 49.1), and median survival appeared similar in patients with and without lung/liver metastasis at baseline (42.6 and 41.1 months, respectively). The most common (≥ 50%) treatment-emergent adverse events were myelosuppression, nausea, and fatigue. No acute drug-related hypertensive events were observed. On the basis of this data, FDA approval was given for the indications listed.]
Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
Radiation Treatment with Azedra (Iobenguane I-131)
Iobenguane I-131 (Azedra)
Azedra (Iobenguane I-131)
1. National Comprehensive Cancer Network (NCCN) Guidelines Version 2.2019 – April 9, 2019. Pancreatic Adenocarcinoma. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) for Pancreatic Adenocarcinoma Version 2.2019©. 2019 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines™ and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org.
2. U.S Food and Drug Administration (FDA). Prescribing information. Azedra® (iobenguane I 131) injection. 2018.
3. van Hulstein LT, Niemeijer ND, Dekkers OM, et al. 131-MIBG therapy for malignant paraganglioma and phaeochromocytoma: systematic review and meta-analysis. Clin Endo. 2013 Oct 1;80(4):487-501.
4. Van Tienhoven, Versteijne E, Suker M, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): a randomized, controlled multicenter phase III trial. ASCO Meeting Library. Presented June 4, 2018.
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy