Last Review Date: 05/04/2023

Date of Origin: 01/01/2012

Dates Reviewed: 12/2011, 02/2013, 11/2013, 06/2014, 05/2015, 04/2016, 04/2017, 04/2018, 05/2019, 05/2020, 05/2021, 05/2022, 05/2023

I. Length of Authorization

Coverage is provided for 6 months and may be renewed.

II. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Ixempra 15 mg single-dose vial powder for injection: 2 vials per 21 days
• Ixempra 45 mg single-dose vial powder for injection: 2 vials per 21 days

2. Max Units (per dose and over time) [HCPCS Unit]:

• 90 billable units every 21 days

III. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ¹

• Patient does not have a history of a severe hypersensitivity to agents containing Cremophor® EL or its derivatives (e.g., polyoxyethylated castor oil); AND
• If used in combination with capecitabine, the patient must not have an AST or ALT >2.5 x ULN or bilirubin >1 x ULN; AND

Breast Cancer † ‡ ^1-4

• Used for recurrent unresectable or metastatic disease OR inflammatory breast cancer with no response to preoperative systemic therapy ‡; AND
  • Patient has human epidermal growth factor receptor 2 (HER2)-negative* disease as confirmed by an FDA-approved or CLIA-compliant testv; AND
    • Used as a single agent; AND

• • • Patient has hormone-receptor positive disease with visceral crisis or refractory to endocrine therapy; AND

• • • Used as first-line therapy if no germline BRCA 1/2 mutation; OR
    • Used as second-line therapy if not a candidate for fam-trastuzumab deruxtecan-nxki; OR
    • Used as third-line therapy and beyond; OR

• • • Patient has triple-negative breast cancer (TNBC) Ψ; AND

• • • Used as first-line therapy if PD-L1 CPS <10 and no germline BRCA 1/2 mutation; OR
    • Used as subsequent therapy; OR
  • Patient has HER2-positive** disease as confirmed by an FDA-approved or CLIA-compliant testv; AND

• Used as fourth-line therapy and beyond in combination with trastuzumab ‡; OR

• Patient has locally advanced or metastatic disease †; AND
  • Patient has failed or is resistant*** to treatment with an anthracycline and a taxane OR patient is taxane resistant and further anthracycline therapy is contraindicated; AND

• • Used in combination with capecitabine; OR
  • Used as a single agent after failure on capecitabine

***Note: Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting. Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting.

v If confirmed using an FDA approved assay – http://www.fda.gov/companiondiagnostics

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

IV. Renewal Criteria ¹

Coverage may be renewed based on the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in Section III; AND
• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: peripheral neuropathy (sensory and motor neuropathy), myelosuppression (e.g., neutropenia, leukopenia, anemia, thrombocytopenia, etc.), toxicity in patients with hepatic impairment, hypersensitivity reactions (including anaphylaxis), cardiac adverse reactions (e.g., myocardial ischemia and ventricular dysfunction), etc.

V. Dosage/Administration ^1-4

VI. Billing Code/Availability Information

HCPCS Code:

• J9207 – Injection, ixabepilone, 1 mg; 1 billable unit = 1 mg

NDC(s):

• Ixempra 15 mg single-dose powder for injection: 70020-1910-xx
• Ixempra 45 mg single-dose powder for injection: 70020-1911-xx

VII. References

1. Ixempra [package insert]. Princeton, NJ; R-Pharm US LLC; January 2023. Accessed March 2023.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for ixabepilone. National Comprehensive Cancer Network, 2023. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed March 2023.
3. Thomas ES, Gomez HL, Li RK, et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. doi: 10.1200/JCO.2007.12.6557.
4. Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007 Aug 10;25(23):3407-14. doi: 10.1200/JCO.2006.09.3849.
5. Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Arch Pathol Lab Med. 2018 Nov;142(11):1364-1382. doi: 10.5858/arpa.2018-0902-SA. Epub 2018 May 30. Arch Pathol Lab Med. 2018. PMID: 29846104.
6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer, Version 4.2023. National Comprehensive Cancer Network, 2023. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed April 2023.
7. Allison KH, Hammond EH, Dowsett M, et al. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. J Clin Oncol 38:1346-1366.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A