Subject:
Ixabepilone (Ixempra)
Description:
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IMPORTANT NOTE:
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.
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Ixempra (ixabepilone) is a microtubule inhibitor that is indicated for the treatment of metastatic or locally advanced breast cancer in combination with capecitabine, in patients who have failed an anthracycline and a taxane.
The safety and efficacy of Ixempra for this indication was established in an open-label, multicenter, multinational, randomized trial of 752 patients with metastatic or locally advanced breast cancer. Patients were eligible for the study if they had tumor progression or resistance to taxanes and anthracycline therapy. The efficacy and safety of Ixempra 40mg/m2 every 3 weeks in combination with capecitabine at 1000mg/m2 twice daily for 2 weeks (followed by 1 week rest) were assessed in comparison with capecitabine monotherapy (1250 mg/m2 twice daily for 2 weeks followed by 1 week rest). The primary endpoint of the study was progression free survival defined as time from randomization to radiologic progression as determined by Independent Radiologic Review, clinical progression of measurable skin lesions or death from any cause. Other study endpoints included objective tumor response based on RECIST, time to response, response duration, and overall survival. Ixempra in combination with capecitabine resulted in a statistically significant improvement in PFS compared to capecitabine alone. Patients receiving combination therapy had a median PFS of 5.7 months, compared to that of 4.1 months in patients receiving monotherapy of capecitabine. The ORR of combination therapy is 34.7% compared to 14.3% in capecitabine monotherapy treated group.
Ixempra as monotherapy is indicated for the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline, a taxane, and capecitabine. Ixempra was evaluated as a single agent in a multicenter single-arm study in 126 women with metastatic or locally advanced breast cancer. Patients were eligible to enroll if they have disease that recurred or progressed following 2 or more chemotherapy regimens including an anthracycline, a taxane, and capecitabine. The study dose of Ixempra was 40 mg/m2 IV infusion over 3 hours every 3 weeks. The primary endpoint was objective tumor response rate and was determined by independent radiologic and investigator review using RECIST. Objective tumor response rate was 12.4% in IRR assessment and 18.3% in investigator assessment. Time to response was 6.1 months and median duration of response was 6.0 months.
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
I. Ixempra is considered medically necessary for the following FDA-approved indication when ALL of the following criteria are met:
a. Metastatic or locally advanced breast cancer
i. Member is 18 years or older, AND
ii. Member has failed therapy with anthracycline AND a taxane, AND
iii. Ixempra must be used in combination with capecitabine, OR
iv. Ixempra must be used as a single agent after failure with capecitabine AND
v. Member does not have any FDA labeled contraindications to the requested agent (e.g. hypersensitivity to drugs formulated with Cremophor EL, baseline neutrophil count <1500 cells/mm3 or a platelet count <100,000 cells/mm3, members with AST or ALT >2.5 X ULN or bilirubin >1 X ULN must not be treated with Ixempra in combination with capecitabine) AND
vi. The prescriber is a specialist in the area of the patient's diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient's diagnosis
II. If medically necessary, Ixempra will be approved for an initial 6 months at the FDA-approved dose of 40mg/m2 administered intravenously over 3 hours every 3 weeks.
[INFORMATIONAL NOTE: Doses for patients with BSA greater than 2.2m2 should be calculated based on 2.2 m2.
See following table for dose modifications:
Ixempra monotherapy or combination therapy | Dose modification |
| Grade 2 neuropathy (moderate) lasting ≥7 days | Decrease dose by 20% |
| Grade 3 neuropathy (severe) lasting | Decrease dose by 20% |
| Grade 3 neuropathy (severe) lasting ≥7 days or disabling neuropathy | Discontinue treatment |
| Any grade 3 toxicity (severe) other than neuropathy | Decrease dose by 20% |
| Transient grade 3 arthralgia/myalgia or fatigue Grade 3 hand-foot syndrome (palmar-plantar erythrodysesthesia) | No change in dose of Ixempra |
| Any grade 4 toxicity (disabling) | Discontinue treatment |
| Neutrophil <500 cells/mm3 for at least 7 days | Decrease dose by 20% |
| Febrile neutropenia | Decrease dose by 20% |
| Platelets <25,000/mm3 or platelets <50,000/mm3 with bleeding | Decrease dose by 20%] |
III. If medically necessary, Ixempra will be approved for continued use annually at the above FDA approved dose if ALL of the following criteria are met:
a. Member continues to meet initial approval criteria, AND
b. Tumor response with stabilization of disease or decrease in size of tumor of tumor spread
c. Absence of unacceptable toxicity (e.g. peripheral neuropathy, myelosuppression, hepatic impairment, hypersensitivity reactions, etc.)
IV. Ixempra is considered medically necessary for the following off-label indications
a. Invasive breast cancer
i. Single agent for recurrent or stage IV HER2-negative disease
1. hormone receptor-negative OR
2. hormone receptor-positive with visceral crisis or endocrine therapy refractory
ii. Therapy in combination with trastuzumab for recurrent or stage IV HER2 positive disease
1. hormone receptor-negative OR
2. hormone receptor-positive with visceral crisis or endocrine therapy refractory
V. Other uses of Ixempra are considered investigational, including but not limited to epithelial ovarian cancer, peritoneal cancer, fallopian tube cancer, recurrent endometrial cancer, renal cell carcinoma, non-small cell lung cancer.
Medicare Coverage:
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.
Medicaid Coverage:
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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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.
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Index:
Ixabepilone (Ixempra)
Ixempra (Ixabepilone)
References:
1. Ixempra [package insert]. R-Pharma US,. Princeton, NJ. January 2016.
2. MICROMEDEX® 2.0 (Healthcare Series). DRUGDEX® Evaluations. Ixempra. Available at: http://www.thomsonhc.com. Accessed Feb 26, 2020.
3. ClinicalTrials.gov. Ixempra. Available at https://clinicaltrials.gov/ct2/results?cond=&term=ixempra&cntry=&state=&city=&dist=. Accessed Feb 26, 2020.
4. National Comprehensive Cancer Network NCCN Drugs & Biologics Compendium. Ixempra. Available at https://www.nccn.org/professionals/drug_compendium/content/. Accessed Feb 26, 2020.
Codes:
(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.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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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
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