Last Review Date: 03/05/2024

Date of Origin: 02/07/2013

Dates Reviewed: 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 02/2017, 05/2017, 08/2017, 11/2017, 2/2018, 5/2018, 09/2018, 12/2018, 03/2019, 06/2019, 9/2019, 12/2019, 03/2020, 06/2020, 09/2020, 03/2022, 03/2023, 03/2024

1. Length of Authorization

Coverage will be provided for 6 months and may be renewed.

2. Dosing Limits

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

• Zaltrap 100 mg/4 mL injection: 2 vials per 28 days
• Zaltrap 200 mg/8 mL injection: 4 vials per 28 days

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

• 500 billable units every 14 days

3. 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 recent history of severe hemorrhage; AND
• Ziv-aflibercept will be not administered for at least 4 weeks following major surgery; AND
• Patient does not have a surgical wound that has not fully healed; AND

Colorectal Cancer (CRC) † ‡ ^1,2,6,8

• Patient has metastatic disease that is resistant to or has progressed following an oxaliplatin-containing regimen (e.g., FOLFOX, CapeOX) †; AND

• Used in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan); OR

• Used as initial treatment for patients with unresectable metastases; AND
  • Patient previously received FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months; AND

• Used in combination with irinotecan or FOLFIRI; AND
  • Patient has mismatch repair proficient/microsatellite-stable (pMMR/MSS) disease; OR

• Used as subsequent therapy for progression of advanced or metastatic disease; AND
  • Patient has not been previously treated with irinotecan-based therapy; AND

• Used in combination with irinotecan or FOLFIRI; AND
  • Patient has mismatch repair proficient/microsatellite-stable (pMMR/MSS) disease; OR
  • Patient has mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
    • • • • Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy

Appendiceal Adenocarcinoma ‡ ²

• Used as subsequent therapy for progression of advanced or metastatic disease; AND
• Patient has not previously been treated with irinotecan-based therapy or oxaliplatin; AND
• Used in combination with irinotecan or FOLFIRI; AND
  • Patient has mismatch repair proficient/microsatellite-stable (pMMR/MSS) disease; OR
  • Patient has mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
    • • • • Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy

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

4. Renewal Criteria ^1,2

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and indication-specific criteria as identified in section III; AND
• Disease response with treatment as defined by stabilization of disease or decrease in size or spread of tumor; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: hemorrhage, gastrointestinal perforation, fistula formation, uncontrolled hypertension (e.g., hypertensive crisis, hypertensive encephalopathy), impaired wound healing, arterial thromboembolic events, proteinuria (e.g., nephrotic syndrome, thrombotic microangiopathy, proteinuria ≥ 2g/24 hours), neutropenia and neutropenic complications, reversible posterior leukoencephalopathy syndrome (RPLS), severe diarrhea/dehydration, etc.

5. Dosage/Administration ^1,2,8

6. Billing Code/Availability Information

HCPCS Code:

• J9400 – Injection, ziv-aflibercept, 1 mg; 1 billable unit = 1 mg

NDC(s):

• Zaltrap 100 mg/4 mL solution, single-dose vial: 00024-5840-xx
• Zaltrap 200 mg/8 mL solution, single-dose vial: 00024-5841-xx

7. References

1. Zaltrap [package insert]. Bridgewater, NJ; Sanofi-Aventis U.S. LLC; December 2023. Accessed January 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) ziv-aflibercept. National Comprehensive Cancer Network, 2024.  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 January 2024.
3. Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.
4. Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf
5. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
6. Tabernero J, Paccard C, Chiron M, et al. Placental growth factor and the angiogenic environment based on analysis of baseline plasma biomarkers from the VELOUR trial.  Journal of Clinical Oncology35, no. 4_suppl(February 01, 2017)592-592. DOI: 10.1200/JCO.2017.35.4_suppl.592
7. Sanofi. A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients With Metastatic Colorectal Cancer (MCRC) Treated With Irinotecan / 5-FU Combination (FOLFIRI) After Failure of an Oxaliplatin Based Regimen. Available from: https://clinicaltrials.gov/ct2/show/NCT00561470?term=NCT00561470&draw=2&rank=1. ClinicalTrials.gov Identifier: NCT00561470. Accessed January 2024.
8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 4.2023. 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 January 2024.

Appendix 1 – Covered Diagnosis Codes

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

The preceding information is intended for non-Medicare coverage determinations. 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 Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

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