Description 
Bavencio is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 

The U.S. Food and Drug Administration (FDA) has approved the immunotherapy drug Bavencio (avelumab) to treat people with advanced urothelial carcinoma, the most common type of bladder cancer. The new approval was based on a clinical trial of 242 people with advanced bladder cancer that grew or spread despite chemotherapy. Among 30 people who were followed for at least 13 weeks, 13.3% saw their tumors shrink. Among 26 people who were followed for at least 6 months, 16.1% saw their tumors shrink. However, 6% of study participants died from an adverse reaction. The study is still ongoing. 

Policy
Merkel cell carcinoma:
The use of avelumab is considered MEDICALLY NECESSARY for the treatment of metastatic Merkel cell carcinoma when all of the following criteria are met:

1. Individual is 12 years of age or older; and
2. Has a current Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 2; and
3. Has not received treatment with another PD-1 agent (for example, nivolumab or pembrolizumab); and
4. Not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Urothelial carcinoma:
The use of avelumab is considered MEDICALLY NECESSARY for the treatment of locally advanced, metastatic or recurrent urothelial carcinoma when all of the following criteria are met:

1. Being used as a single agent: and
2. Individual meets one of the following criteria:
   1. Has demonstrated disease progression on or after platinum-containing chemotherapy: or
   2. Has demonstrated disease progression within 12 months of receiving neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; and
   3. Used as maintenance treatment of locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy; and
3. Has a current ECOG performance status of 0 – 2; and
4. Has not received treatment with another PD-1 agent (for example, nivolumab or pembrolizumab); and
5. Not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Renal cell carcinoma:
The use of avelumab is considered MEDICALLY NECESSARY for the treatment of advanced renal cell carcinoma when all of the following criteria are met:

1. Being used in combination with axitinib
2. Has a current ECOG performance status of 0 – 2; and
3. Has not received treatment with another PD-1 agent (for example, nivolumab or pembrolizumab); and
4. Not receiving therapy for an autoimmune disease or chronic condition requiring treatment with a systemic immunosuppressant.

Gestational trophoblastic neoplasia, chemotherapy-resistant:

1. Prescribed as a single agent following failure of ≥ 2 systemic chemotherapeutic agents

Investigational:
The use of avelumab is considered investigational and/or unproven and is therefore considered NOT MEDICALLY NECESSARY when the above criteria are not met and for all other uses. 

 Uses and indications of injectable oncology medications (including chemotherapy/systemic therapy, therapeutic radiopharmaceuticals and selected supportive therapies) are MEDICALLY NECESSARY if they are listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence + Consensus of 1, 2A and 2B. Treatments listed with a Category of Evidence and Consensus of 3 are considered unproven and NOT MEDICALLY NECESSARY.

Definitions 
Disease progression: Cancer that continues to grow or spread.

ECOG Performance Status: A scale used to determine the individual's level of functioning. This scale may also be referred to as the WHO (World Health Organization) or Zubrod score which is based on the following scale:

• 0 = Fully active, able to carry on all pre-disease performance without restriction
• 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
• 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
• 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
• 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
• 5 = Dead

Merkel cell carcinoma: A rare, aggressive skin cancer.

Metastasis: A cancer that has spread from one part of the body to another; a metastatic tumor contains cells that are like those in the original (primary) tumor and have spread beyond the local lymph nodes.

Monoclonal antibody: A protein developed in the laboratory that can locate and bind to specific substances in the body and on the surface of cancer cells.

Urothelial carcinoma: A type of bladder cancer which occurs in the urinary tract system.

References 

1. Apolo AB, Infante JR, Balmanoukian A, et al. Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase Ib study. J Clin Oncol. 2017 Apr 4:JCO2016716795. [Epub ahead of print].
2. Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017; 17(4):515-523.
3. 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; 17(10):1374-1385.
4. Llombart B, Kindem S, Chust M. Merkel Cell Carcinoma: An update of key imaging techniques, prognostic factors, treatment, and follow-up. Actas Dermosifiliogr. 2017; 108(2):98-107.
5. Nghiem P, Kaufman HL, Bharmal M, et al. Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma. Future Oncol. 2017 Mar 28. 
6. American Cancer Society. Cancer facts & figures 2017. Atlanta: American Cancer Society; 2017.
7. Avelumab [Product Information]. New York, NY. Pfizer; May 9, 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761078s000lbl.pdf . Accessed on May 30, 2017.
8. NCCN Clinical Practice Guidelines in Oncology^® . © 2017 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on May 25, 2017.
   • Bladder Cancer (V.5.2017). Revised May 25, 2017.
   • Merkel Cell Carcinoma (V.1.2017). Revised October 3, 2016.
9. Bavencio (avelumab) [Prescribing Information]. EMD Serano. May 2017.
10. National Institutes of Health, U.S. National Library of Medicine, Daily Med. Available at https://dailymed.nlm.nih.gov/dailymed/advanced-search.cfm. Accessed May, 2017
11. Lemos B, Storer B, Iyer J, et al. Pathologic Nodal Evaluation Improves Prognostic Accuracy in Merkel Cell Carcinoma: Analysis of 5,823 Cases as the Basis of the First Consensus Staging System for this Cancer. Journal of the American Academy of Dermatology. 2010;63(5):751–761.
12. Clinicaltrials.gov. Avelumab for treatment of Metastatic Merkel Cell Carcinoma. Available at: clinicaltrials.gov. Accessed on March 28, 2017.
13. NCCN MCC Guidelines® NCCN Clinical Practice ® Version 1. 2017. Merkel cell carcinoma. https://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf. Accessed May 5, 2017.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, and other unaffliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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