Last Review Date: 10/03/2024

Date of Origin: 04/25/2017

Dates Reviewed: 04/2017, 05/2017, 08/2017, 11/2017, 02/2018, 05/2018, 09/2018, 11/2018, 03/2019, 06/2019, 09/2019, 12/2019, 03/2020, 06/2020, 08/2020, 12/2020, 03/2021, 06/2021, 09/2021, 12/2021, 03/2022, 06/2022, 09/2022, 12/2022, 03/2023, 06/2023, 09/2023, 12/2023, 03/2024, 07/2024, 10/2024

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]:

• Bavencio 200 mg/10 mL single-dose vial: 4 vials per 14 days

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

• 80 billable units (800 mg) every 14 days (all indications)

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age, unless otherwise indicated; AND

Universal Criteria

• Patient has not received previous therapy with a programmed death (PD-1/PD-L1)-directed therapy (e.g., nivolumab, pembrolizumab, dostarlimab, atezolizumab, durvalumab, cemiplimab, nivolumab/relatlimab, retifanlimab, tislelizumab, toripalimab, etc.), unless otherwise specified ^Δ; AND

Merkel Cell Carcinoma (MCC) † ‡ Ф ^1,2,4,5

• Patient is at least 12 years of age; AND
• Used as single-agent therapy; AND
  • Patient has primary locally advanced disease ‡; AND
    • Both curative surgery and curative radiation therapy are not feasible; OR
    • Patient has had disease progression on neoadjuvant nivolumab therapy; OR

• • Patient has metastatic disease; OR
  • Patient has recurrent locally advanced or recurrent regional disease ‡; AND
    • Both curative surgery and curative radiation therapy are not feasible

Urothelial Carcinoma (Bladder Cancer) † ‡ ^1,4,6,8,16

• Used as single-agent therapy; AND
  • Patient has one of the following diagnoses:
    • Locally advanced or metastatic urothelial carcinoma †
    • Muscle invasive bladder cancer with local recurrence or persistent disease in a preserved bladder treated with curative intent ‡
    • Metastatic or local bladder cancer recurrence post cystectomy treated with curative intent ‡
    • Metastatic upper genitourinary (GU) tract tumors ‡
    • Metastatic urothelial carcinoma of the prostate ‡
    • Recurrent or metastatic primary carcinoma of the urethra (excluding recurrence of clinical stage T3-4 disease or palpable inguinal lymph nodes) ‡; AND

• Used for disease that progressed during or following platinum-containing chemotherapy*; OR
• Used as second-line treatment after chemotherapy other than a platinum; OR
  • Used as first-line maintenance treatment †; AND
    • Patient has locally advanced or metastatic urothelial carcinoma (inclusive of bladder, upper GU tract, urethra, and/or prostate cancer); AND
    • Patient has not progressed with first-line platinum-containing chemotherapy

Renal Cell Carcinoma (RCC) † ‡ ^1,4,9,14

• Used in combination with axitinib; AND
• Used as first-line therapy; AND
• Used for the treatment of advanced, relapsed, or stage IV* disease and clear cell histology

*When used as first line therapy for stage IV disease, disease must be M1 or unresectable T4, M0

Gestational Trophoblastic Neoplasia ‡ ^4,13,15

• Used as single-agent therapy for multiagent chemotherapy-resistant disease; AND
  • Patient has intermediate placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT); AND
    • Patient has recurrent or progressive disease; OR
  • Patient has high-risk disease (i.e., prognostic score ≥ 7 or FIGO stage IV disease)

Endometrial Carcinoma (Uterine Neoplasms) ‡ ^4,18

• Used as single-agent therapy; AND
• Patient has recurrent disease; AND
• Used as subsequent therapy for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors

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

4. Renewal Criteria ^{Δ  1}

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria 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: severe or life-threatening infusion-related reactions, severe immune-mediated adverse reactions (e.g., pneumonitis, hepatotoxicity/hepatitis, colitis, endocrinopathies, nephritis with renal dysfunction, dermatitis/dermatologic adverse reactions, etc.), major adverse cardiovascular events (MACE) when used in combination with axitinib, complications of allogeneic hematopoietic stem cell transplantation (HSCT), etc.

5. Dosage/Administration ^1,13,18

6. Billing Code/Availability Information

HCPCS Code:

• J9023 – Injection, avelumab, 10 mg; 1 billable unit = 10 mg

NDC:

• Bavencio 200 mg/10 mL single-dose vial: 44087-3535-xx

7. References

1. Bavencio [package insert]. Rockland, MA; EMD Serono, Inc; March 2024. Accessed September  2024.
2. Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016 Oct;17(10):1374-1385.
3. Novakovic AM, Wilkins JJ, Dai H, et al. Changing body weight-based dosing to a flat dose for avelumab in metastatic Merkel cell and advanced urothelial carcinoma. Clin Pharmacol Ther. 2019 Sep 25.
4. Referenced with permission from the NCCN Drugs and Biologics Compendium (NCCN Compendium®) avelumab. 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 September 2024.
5. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Merkel Cell Carcinoma. Version 1.2024. 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 September 2024.
6. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Bladder Cancer. Version 4.2024. 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 September 2024.
7. Gupta S, Sonpavde G, Grivas P, et al. Defining “platinum-ineligible” patients with metastatic urothelial cancer (mUC). J Clin Oncol. 2019 Mar 1;37(7_suppl):451.
8. Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol. 2018 Jan;19(1):51-64. Doi: 10.1016/S1470-2045(17)30900-2. Epub 2017 Dec 5.
9. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1103-1115. Doi: 10.1056/NEJMoa1816047. Epub 2019 Feb 16.

10. 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.
11. Hematology/Oncology Pharmacy Association (2022). Intravenous Cancer Drug Waste Issue Brief. Retrieved from: https://www.hoparx.org/documents/65/HOPA_Drug_Waste_Issue_Brief_-_Updated_01.19.22_FINAL.pdf
12. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
13. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Gestational Trophoblastic Neoplasia. Version 2.2024. 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 September 2024.
14. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Kidney Cancer. Version 2.2025. 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 September 2024.
15. You B, Bolze PA, Lotz JP, et al. Avelumab in Patients With Gestational Trophoblastic Tumors With Resistance to Single-Agent Chemotherapy: Cohort A of the TROPHIMMUN Phase II Trial. J Clin Oncol. 2020 Sep 20;38(27):3129-3137. Doi: 10.1200/JCO.20.00803. Epub 2020 Jul 27.
16. Powles T, Park SH, Voog E, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. Doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18. PMID: 32945632.
17. Bellmunt, J. (2024). Treatment of metastatic urothelial cancer of the bladder and urinary tract. In Lerner SP, Shah S (Eds.), UptoDate. Last updated July 17, 2024. Accessed September 6, 2024. Available from https://www.uptodate.com/contents/treatment-of-metastatic-urothelial-cancer-of-the-bladder-and-urinary-tract?search=cisplatin%20ineligible&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1.
18. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Uterine Neoplasms. Version 2.2024. 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 September 2024.
19. Galsky MD, Balar AV, Black PC, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of urothelial cancer. Journal for ImmunoTherapy of Cancer 2021;9:e002552. doi: 10.1136/jitc-2021-002552.
20. Gupta S, Bellmunt J, Plimack ER, et al. Defining “platinum-ineligible” patients with metastatic urothelial cancer (mUC). J Clin Oncol. 2022 June 1;40(16_suppl):4577.
21. You B, Bolze PA, Lotz JP, et al. Avelumab in patients with gestational trophoblastic tumors with resistance to polychemotherapy: Cohort B of the TROPHIMMUN phase 2 trial. Gynecol Oncol. 2023 Jan;168:62-67. doi: 10.1016/j.ygyno.2022.11.005.

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