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Ixempra® (ixabepilone) (Intravenous)

Policy Number: VP-0072

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

FOR PEEHIP Members Only -Coverage excludes the provider-administered medication(s) outlined in this drug policy from being accessed through a specialty pharmacy. It must be obtained through buy and bill.

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
  1. 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.

*HER2-negative expression criteria: 5,6

  • Immunohistochemistry (IHC) assay is 0 or 1+; OR
  • Dual-probe in situ hybridization (ISH) assay indicating (Group 5) HER2/CEP17 ratio <2.0 AND average HER2 copy number <4.0 signals/cell; OR
  • Concurrent dual-probe ISH and IHC assay results indicating one of the following:
  • (Group 2) HER2/CEP17 ratio ≥2.0 AND average HER2 copy number <4.0 signals/cell and concurrent IHC 0-1+ or 2+; OR
  • (Group 3) HER2/CEP17 ratio <2.0 AND average HER2 copy number ≥6.0 signals/cell and concurrent IHC 0-1+; OR
  • (Group 4) HER2/CEP17 ratio <2.0 AND average HER2 copy number ≥4.0 and <6.0 signals/cell and concurrent IHC 0-1+ or 2+

Ψ ER/PR-negative expression criteria: 7

  • Immunohistochemistry (IHC) assay: Sample is considered ER/PR negative if the percentage of cancer cells staining on evaluation is <1% OR 0% of tumor cell nuclei are immunoreactive

Note: A sample may be deemed uninterpretable for ER or PR if the sample is inadequate (insufficient cancer or severe artifacts present, as determined at the discretion of the pathologist), if external and internal controls (if present) do not stain appropriately, or if pre-analytic variables have interfered with the assay’s accuracy.

Ψ ER Scoring Interpretation (following ER testing by validated IHC assay)

Results

Interpretation

  • 0% – <1% of nuclei stain
  • ER-negative
  • 1%–10% of nuclei stain
  • ER-low–positive*
  • >10% of nuclei stain
  • ER-positive

*Note: Patients with cancers with ER-low–positive (1%–10%) results are a heterogeneous group with reported biologic behavior often similar to ER-negative cancers; thus, as such these cancers inherently behave aggressively and may be treated similar to triple-negative disease. Individualized consideration of risks versus benefits should be incorporated into decision-making.

**HER2-positive overexpression criteria: 5,6

  • Immunohistochemistry (IHC) assay 3+; OR
  • Dual-probe in situ hybridization (ISH) assay HER2/CEP17 ratio2.0 AND average HER2 copy number 4.0 signals/cell; OR
  • Dual-probe in situ hybridization (ISH) assay AND concurrent IHC indicating one of the following:
          • HER2/CEP17 ratio 2.0 AND average HER2 copy number < 4.0 signals/cell AND concurrent IHC 3+; OR
          • HER2/CEP17 ratio < 2.0 AND average HER2 copy number 6.0 signals/cell AND concurrent IHC 2+ or 3+; OR
    • HER2/CEP17 ratio < 2.0 AND average HER2 copy number ≥ 4.0 and < 6.0 signals/cell AND concurrent IHC 3+

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

Indication

Dose

Breast Cancer

Administer 40 mg/m² intravenously (IV) over 3 hours every 21 days.

(Doses for patients with a BSA > 2.2 m2 should be calculated based on 2.2 m2)

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

ICD-10

ICD-10 Description

C50.011

Malignant neoplasm of nipple and areola, right female breast

C50.012

Malignant neoplasm of nipple and areola, left female breast

C50.019

Malignant neoplasm of nipple and areola, unspecified female breast

C50.021

Malignant neoplasm of nipple and areola, right male breast

C50.022

Malignant neoplasm of nipple and areola, left male breast

C50.029

Malignant neoplasm of nipple and areola, unspecified male breast

C50.111

Malignant neoplasm of central portion of right female breast

C50.112

Malignant neoplasm of central portion of left female breast

C50.119

Malignant neoplasm of central portion of unspecified female breast

C50.121

Malignant neoplasm of central portion of right male breast

C50.122

Malignant neoplasm of central portion of left male breast

C50.129

Malignant neoplasm of central portion of unspecified male breast

C50.211

Malignant neoplasm of upper-inner quadrant of right female breast

C50.212

Malignant neoplasm of upper-inner quadrant of left female breast

C50.219

Malignant neoplasm of upper-inner quadrant of unspecified female breast

C50.221

Malignant neoplasm of upper-inner quadrant of right male breast

C50.222

Malignant neoplasm of upper-inner quadrant of left male breast

C50.229

Malignant neoplasm of upper-inner quadrant of unspecified male breast

C50.311

Malignant neoplasm of lower-inner quadrant of right female breast

C50.312

Malignant neoplasm of lower-inner quadrant of left female breast

C50.319

Malignant neoplasm of lower-inner quadrant of unspecified female breast

C50.321

Malignant neoplasm of lower-inner quadrant of right male breast

C50.322

Malignant neoplasm of lower-inner quadrant of left male breast

C50.329

Malignant neoplasm of lower-inner quadrant of unspecified male breast

C50.411

Malignant neoplasm of upper-outer quadrant of right female breast

C50.412

Malignant neoplasm of upper-outer quadrant of left female breast

C50.419

Malignant neoplasm of upper-outer quadrant of unspecified female breast

C50.421

Malignant neoplasm of upper-outer quadrant of right male breast

C50.422

Malignant neoplasm of upper-outer quadrant of left male breast

C50.429

Malignant neoplasm of upper-outer quadrant of unspecified male breast

C50.511

Malignant neoplasm of lower-outer quadrant of right female breast

C50.512

Malignant neoplasm of lower-outer quadrant of left female breast

C50.519

Malignant neoplasm of lower-outer quadrant of unspecified female breast

C50.521

Malignant neoplasm of lower-outer quadrant of right male breast

C50.522

Malignant neoplasm of lower-outer quadrant of left male breast

C50.529

Malignant neoplasm of lower-outer quadrant of unspecified male breast

C50.611

Malignant neoplasm of axillary tail of right female breast

C50.612

Malignant neoplasm of axillary tail of left female breast

C50.619

Malignant neoplasm of axillary tail of unspecified female breast

C50.621

Malignant neoplasm of axillary tail of right male breast

C50.622

Malignant neoplasm of axillary tail of left male breast

C50.629

Malignant neoplasm of axillary tail of unspecified male breast

C50.811

Malignant neoplasm of overlapping sites of right female breast

C50.812

Malignant neoplasm of overlapping sites of left female breast

C50.819

Malignant neoplasm of overlapping sites of unspecified female breast

C50.821

Malignant neoplasm of overlapping sites of right male breast

C50.822

Malignant neoplasm of overlapping sites of left male breast

C50.829

Malignant neoplasm of overlapping sites of unspecified male breast

C50.911

Malignant neoplasm of unspecified site of right female breast

C50.912

Malignant neoplasm of unspecified site of left female breast

C50.919

Malignant neoplasm of unspecified site of unspecified female breast

C50.921

Malignant neoplasm of unspecified site of right male breast

C50.922

Malignant neoplasm of unspecified site of left male breast

C50.929

Malignant neoplasm of unspecified site of unspecified male breast

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

Medicare Part B Administrative Contractor (MAC) Jurisdictions

Jurisdiction

Applicable State/US Territory

Contractor

E (1)

CA, HI, NV, AS, GU, CNMI

Noridian Healthcare Solutions, LLC

F (2 & 3)

AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ

Noridian Healthcare Solutions, LLC

5

KS, NE, IA, MO

Wisconsin Physicians Service Insurance Corp (WPS)

6

MN, WI, IL

National Government Services, Inc. (NGS)

H (4 & 7)

LA, AR, MS, TX, OK, CO, NM

Novitas Solutions, Inc.

8

MI, IN

Wisconsin Physicians Service Insurance Corp (WPS)

N (9)

FL, PR, VI

First Coast Service Options, Inc.

J (10)

TN, GA, AL

Palmetto GBA, LLC

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA, LLC

L (12)

DE, MD, PA, NJ, DC (includes Arlington & Fairfax counties and the city of Alexandria in VA)

Novitas Solutions, Inc.

K (13 & 14)

NY, CT, MA, RI, VT, ME, NH

National Government Services, Inc. (NGS)

15

KY, OH

CGS Administrators, LLC