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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:152
Effective Date: 08/21/2020
Original Policy Date:05/23/2017
Last Review Date:07/14/2020
Date Published to Web: 05/30/2017
Subject:
Avelumab (Bavencio)

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

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The US Food and Drug Administration (FDA) approved Bavencio® (avelumab) Injection 20 mg/mL, for intravenous use, for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC). This indication is approved under accelerated approval based on tumor response and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Bavencio was developed, reviewed and approved through the FDA’s Breakthrough Therapy Designation and Priority Review programs.

Bavencio, a human anti-PD-L1 antibody, is the first FDA-approved therapy for patients with mMCC. Metastatic MCC is a rare and aggressive skin cancer, with fewer than half of patients surviving more than one year and fewer than 20% surviving beyond five years.

The efficacy and safety of BAVENCIO was demonstrated in the JAVELIN Merkel 200 trial, an open-label, single-arm, multi-center study conducted in 88 patients with histologically confirmed metastatic MCC whose disease had progressed on or after chemotherapy administered for distant metastatic disease. Sixty-five percent of patients were reported to have had one prior anti-cancer therapy for metastatic MCC and 35% had two or more prior therapies. The major efficacy outcome measures were confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) as assessed by a blinded independent central review committee (IRC) and IRC-assessed duration of response
The overall response rate (ORR) was 33% (95% confidence interval [CI]: 23.3–43.8%). Eleven percent of patients experienced a complete response (95% CI: 6.6-19.9%) and 22% of patients experienced a partial response (95% CI: 13.5-31.7%). Tumor responses were durable, with 86% of responses lasting for at least six months (n=25).1 Forty-five percent of responses lasted at least 12 months (n=13). Duration of response ranged from 2.8 to over 23.3 months.

The safety and efficacy of Bavencio was demonstrated in the UC cohorts of the Javelin Solid Tumor trial, an open-label, single-arm, multi-center study that included 242 patients with locally advanced or metastatic urothelial carcinoma (UC) with disease progression on or after platinum-containing chemotherapy regimen or who had disease progression within 12 months of treatment with platinum-containing neoadjuvant or adjuvant chemotherapy. Patients with active or history of central nervous system metastasis; other malignancies within the last 5 years; organ transplant; conditions requiring therapeutic immune suppression; or active infection with HIV, hepatitis B, or hepatitis C were excluded. Patients with autoimmune disease, other than type 1 diabetes, vitiligo, psoriasis, or thyroid disease that did not require immunosuppressive treatment, were excluded. Patients were included regardless of their PD-L1 status.

The warnings and precautions for Bavencio include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions), infusion-related reactions and embryo-fetal toxicity. The most common adverse reactions (reported in at least 20% of patients) included fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reactions (22%), rash (22%), decreased appetite (20%) and peripheral edema (20%).

In May 2019, Bavencio was FDA approved for first-line treatment, in combination with axitinib of patients with advanced renal cell carcinoma. The efficacy and safety of Bavencio in combination with axitinib was demonstrated in the JAVELIN Renal 101 trial (NCT02684006), a randomized, multicenter, open-label, study of Bavencio in combination with axitinib in 886 patients with untreated advanced RCC regardless of tumor PD-L1 expression [intent-to-treat (ITT) population]. Patients with autoimmune disease or conditions requiring systemic immunosuppression were excluded. Patients were randomized (1:1) to one of the following treatment arms: Bavencio 10 mg/kg intravenous infusion every 2 weeks in combination with axitinib 5 mg twice daily orally (N=442) or Sunitinib 50 mg once daily orally for 4 weeks followed by 2 weeks off (N=444). The major efficacy outcome measures were progression-free survival (PFS), as assessed by an BICR using RECIST v1.1 and overall survival (OS) in patients with PD-L1-positive tumors using a clinical trial assay (PD-L1 expression level ≥ 1%). Since PFS was statistically significant in patients with PD-L1-positive tumors [HR 0.61 (95% CI: 0.48, 0.79)], it was then tested in the ITT population and a statistically significant improvement in PFS in the ITT population was also demonstrated.

On June 30, 2020, the FDA approved Bavencio for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. Efficacy of avelumab for maintenance treatment of UC was investigated in the JAVELIN Bladder 100 trial (NCT02603432), a randomized, multi-center, open-label trial that enrolled 700 patients with unresectable, locally advanced or metastatic urothelial carcinoma that had not progressed with four to six cycles of first-line platinum-containing chemotherapy. Patients were randomized (1:1) to receive either avelumab intravenously every 2 weeks plus best supportive care (BSC) or BSC alone. Treatment was initiated within 4-10 weeks after last chemotherapy dose. The main efficacy outcome measures were overall survival (OS) in all patients and in patients with PD-L1-positive tumors. The median OS in all patients was 21.4 months in the avelumab arm and 14.3 months in the BSC alone arm (HR: 0.69; 95%CI: 0.56, 0.86; p=0.001). Among patients with PD-L1-positive tumors (51%), the HR for OS was 0.56 (95% CI: 0.40, 0.79; p<0.001). In an exploratory analysis of patients with PD- L1- negative tumors (39%), the OS hazard ratio was 0.85 (95% CI: 0.62, 1.18). The most common adverse reactions in > 20% of patients who received avelumab were fatigue, musculoskeletal pain, urinary tract infection, and rash. One patient died from sepsis and 28% of patients had serious adverse reactions. The recommended avelumab dose is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. The results from this study supported the conversion of accelerated approval of avelumab to a regular approval.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

The requirements of the Horizon BCBSNJ Avelumab (Bavencio) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

1. Bavencio (avelumab) is medically necessary for the treatment of metastatic Merkel Cell carcinoma (mMCC), locally advanced or metastatic urothelial carcinoma (UC) or advanced renal cell carcinoma (RCC) when ALL of the following criteria are met:


    a. Documentation that member has one of the following diagnosis:

      i. Metastatic Merkel Cell Carcinoma; AND

      1. Member is at least 12 years old and older; AND

          2. Member must have failed at least one line of adequately (at least 2 cycles) dosed chemotherapy and has subsequently progressed; OR

            [INFORMATION NOTE: NCCN Clinical Practice Guidelines for Merkel Cell Carcinoma recommends any of these chemotherapy agents; Cisplatin with or without etoposide phosphate, Carboplatin with or without etoposide phosphate, Topotecan and Cyclophosphamide with doxorubicin (or epirubicin) with vincristine (CAV).]
      ii. Locally advanced or metastatic urothelial carcinoma AND

      1. Member is at least 18 years old and older; AND

          2. Member meets one of the following:
            • Member has disease progression during or following platinum-containing chemotherapy OR
            • Member has disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy OR
            • Used as maintenance treatment for members whose disease has not progressed with first-line platinum-containing chemotherapy
      iii. Advanced renal cell carcinoma

      1. Member is at least 18 years old and older; AND

      2. Member will be using as first line treatment, in combination with axitinib AND


    b. Member has no known severe hypersensitivity reaction to monoclonal antibodies; AND

    c. Member must have adequate renal function (defined by an estimated creatinine clearance >50 mL/min according to Cockroft-Gault formula); AND

    d. Member must have adequate hematological function (defined as a WBC count of >3x109/L with an ANC ≥1.5x109/L, lymphocyte count ≥0.5x109/L, platelet count ≥100x109/L, and hemoglobin ≥9 g/dL); AND

    e. Member must have adequate hepatic function (defined as Total serum bilirubin ≤1.5 x ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN) AND

    f. Member does not have any of the following:


      i. History of testing positive for human immunodeficiency virus (HIV) or known AIDS,

      ii. History of testing positive to Hepatitis C or Hepatitis B,

      iii. Active cardiovascular disease such as cerebral vascular accident, myocardial infarction , unstable angina within the last 6 months,

      iv. Active autoimmune disease,

      v. Medical conditions requiring systemic immunosuppression, included but not limited to, methotrexate, azathioprine, cyclosporine; AND


    g. Member is currently not pregnant; AND

    h. Member is currently not being treated with chronic systemic corticosteroids included but limited to prednisone, methylprednisolone.

    i. Member has not received previous therapy with a programmed death (PD-1/PD-L1)-directed therapy (e.g., nivolumab, pembrolizumab, atezolizumab, durvalumab, etc.)

    k. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist, urologist) or has consulted with a specialist in the area of the patient’s diagnosis

    [INFORMATION NOTE: As per the FDA approved package insert, advise females of child brearing age potential to use effective contraception during treatment with Bavencio and for at least one month after the last dose of Bavencio.]


2. When Bavencio (avelumab) is considered medically necessary, initial therapy will be approved for a period of 6 months at the FDA approved dose of 800mg as an intravenous infusion over 60 minutes every 2 weeks.
    • Dosing should be calculated using actual body weight and not flat dosing (as applicable) based on the following:
      • Weight > 60 kg: standard dose 800 mg IV every 2 weeks
      • Weight is ≤ 60 kg: use 600 mg IV every 2 weeks
    • Note: This information is not meant to replace clinical decision making with initiating or modifying medication therapy and should only be used as a guide. Patient-specific variables should be taken into account.

    [INFORMATION NOTE: As per the FDA approved package insert, premedication should be performed with acetaminophen and antihistamine with the first 4 infusions and subsequently thereafter as needed. During clinical trial there was immune-mediated pneumonitis, hepatitis and colitis. Monitor for changes in liver function and withhold for moderate hepatitis. Also, discontinue therapy for severe life threatening hepatitis.

    The clinical trials in the FDA labeled package insert for the indications of Bavencio (metastatic merkel cell carcinoma, locally advanced or metastatic urothelial carcinoma, and advanced renal cell carcinoma) included weight based dosing. The weight based dosing of 10mg/kg IV every 2 weeks was used in the studies for these indications. The weight based dosing of 10mg/kg IV every 2 weeks was compared to the flat dosing of 800mg IV every 2 weeks and doses were shown to provide similar distributions with no advantage to either dosing regimen approach with respect to controlling pharmacokinetic variability.]

3. Continuation of Bavencio (avelumab) will be approved annually at the FDA-approved dose of 800mg as an intravenous infusion every 2 weeks if none of the following occurs:

    a. Member has unacceptable toxicity such as, including but not limited to, ileus, transaminitis, elevated creatinine kinase, pericardial effusion and tubulointerstitial nephritis.

    b. Disease progression such as new or worsening symptoms.


4. Bavencio (avelumab) is considered medically necessary for off-label indications that have in effect a rating of ‘Category 1’ or ‘Category 2A’ in the current recommendations in the National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - avelumab]. Available at: https://www.nccn.org/professionals/drug_compendium/content/.
    5. Bavencio (avelumab) is considered investigational for all other indications.

    Medicare Coverage


    There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage will follow the Horizon Policy.


    Medicaid Coverage

    For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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    Horizon BCBSNJ Medical Policy Development Process:

    This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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    Index:
    Avelumab (Bavencio)
    Bavencio (Avelumab)
    Merkle Cell Carcinoma, Avelumab (Bavencio) for

    References:
    1. Bavencio (avelumab) [Prescribing Information]. EMD Serano. June 2020.

    2. 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

    3. 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.

      4. Clinicaltrials.gov. Avelumab for treatment of Metastatic Merkel Cell Carcinoma. Available at: clinicaltrials.gov. Accessed on March 28, 2017.

      5. NCCN MCC Guidelines® NCCN Clinical Practice ® Version 1. 2020. Merkel cell carcinoma. https://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf. Accessed November 2019.

      6. NCCN MCC Guidelines® NCCN Clinical Practice ® Version 4. 2019. Bladder Cancer. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed November 2019.

      7. Clinicaltrials.gov. Avelumab in metastatic or locally advanced solid tumors (JAVELIN Solid Tumors). Available at https://clinicaltrials.gov/ct2/show/NCT01772004. Accessed February 2019.

      8. National Comprehensive Cancer Network. NCCN Drugs &Biologics Compendium. Bavencio. Available at https://www.nccn.org/professionals/drug_compendium/content/. Accessed June 2020.

      9. ClinicalTrials.gov. Bavencio. Available at https://clinicaltrials.gov/ct2/results?cond=&term=bavencio&cntry=&state=&city=&dist= Accessed November 2019.

      Codes:
      (The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

      CPT*


        C9491
        J9023
      HCPCS

      * CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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      Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

      The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

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