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This is a new policy published on 1/28/2020. It will be effective on 2/29/2020 or later.
  
Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:200
Effective Date: 02/29/2020
Original Policy Date:01/28/2020
Last Review Date:
Date Published to Web: 01/28/2020
Subject:
Enfortumab vedotin-ejfv (Padcev)

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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Padcev (enfortumab vedotin-ejfv) is a nectin-4-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.

The safety and efficacy of Padcev (enfortumab vedotin-ejfv) was evaluated in EV-201 (NCT03219333): a single-arm, multicenter phase 2 trial that enrolled 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy. Patients were excluded if they had active CNS metastases, ongoing sensory or motor neuropathy ≥ Grade 2, or uncontrolled diabetes defined as hemoglobin A1C (HbA1c) ≥8% or HbA1c ≥7% with associated diabetes symptoms.

The median number of prior systemic therapies was 3 (range: 1 to 6). 46% of patients received prior PD-1 inhibitor, 42% received prior PD-L1 inhibitor, and an additional 13% received both PD-1 and PD-L1 inhibitors. 66% of patients received prior cisplatin based regimens, 26% received prior carboplatin-based regimens, and an additional 8% received both cisplatin and carboplatin-based regimens.

Tumor size decreased at least partially for 44% of participants, with 12% achieving a complete response and 32% achieving a partial response. The average response lasted for 7.6 months with a median duration of 10.2 months and a maximum duration of 15.6 months. The most common adverse reactions (≥20%) included fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, dysgeusia, diarrhea, dry eye, pruritus and dry skin.

As per the Food & Drug Administration (FDA), Padcev (enfortumab vedotin-ejfv) received Breakthrough Therapy designation and Priority Review. This indication is approved under accelerated approval based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
    1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis.

    2. Padcev (enfortumab vedotin-ejfv) is considered medically necessary for the treatment of adult patients with locally advanced or metastatic urothelial cancer who meet ALL of the following criteria:

        a. Member has an ECOG performance status score of 0-1

        b. Member has previously received a programmed death receptor-1 (PD-1) OR programmed death-ligand 1 (PD-L1) inhibitor, AND a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting

        c. Member is not currently using any other chemotherapy agents concurrently

        d. Member does not have active central nervous system (CNS) metastases

        e. Member does not have sensory or motor neuropathy Grade ≥2

        f. Member does not have uncontrolled diabetes (defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c ≥7% with associated diabetes symptoms)

        e. Member is not on any immunotherapy related myocarditis, colitis, uveitis, or pneumonitis

        [INFORMATIONAL NOTE: As per the FDA approved package insert warnings & precautions section: Padcev carries a warning for embryo-fetal toxicity: Padcev can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception.]

    3. When Padcev (enfortumab vedotin-ejfv) is considered medically necessary, therapy will initially be approved for 6 months based on FDA-approved dosing:

        • 1.25 mg/kg (up to a maximum of 125 mg for members who are ≥100 kg) administered as an intravenous (IV) infusion over 30 minutes on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity

          [INFORMATIONAL NOTE: as per the FDA approved package insert dosing section: dose modification is as follows:
          Adverse ReactionSeverityDose Modification
          HyperglycemiaBlood glucose >250mg/dLWithhold until elevated blood glucose has improved to ≤ 250 mg/dL, then resume
          treatment at the same dose level.
          Peripheral
          Neuropathy
          Grade 2Withhold until Grade ≤1, then resume treatment at the same dose level (if first occurrence). For a recurrence, withhold until Grade ≤1 then, resume treatment reduced by one dose level.
          Grade ≥3Permanently discontinue.
          Skin ReactionsGrade 3 (severe)Withhold until Grade ≤1, then resume treatment at the same dose level or consider dose reduction by one dose level.
          Grade 4 or recurrent
          Grade 3
          Permanently discontinue.
          Other
          nonhematologic
          toxicity
          Grade 3Withhold until Grade ≤ 1, then resume treatment at the same dose level or consider dose reduction by one dose level
          Grade 4Permanently discontinue.
          Hematologic toxicityGrade 3, or Grade 2
          thrombocytopenia
          Withhold until Grade ≤ 1, then resume treatment at the same dose level or consider dose reduction by one dose level.
          Grade 4Withhold until Grade ≤ 1, then reduce dose by one dose level or discontinue treatment.
          Dose Level
          Starting dose1.25mg/kg up to 125mg
          First dose reduction1.0 mg/kg up to 100mg
          Second dose reduction0.75mg/kg up to 75mg
          Third dose reduction0.5mg/kg up to 50mg]

    4. Continued therapy with Padcev (enfortumab vedotin-ejfv) for treatment of adult patients with locally advanced or metastatic urothelial cancer will be approved every 6 months if the member meets ALL of the following criteria:
      • Member shows treatment response shown by decrease in tumor size/tumor spread
      • There is absence of intolerable adverse effects (e.g.: uncontrolled hyperglycemia, peripheral neuropathy, ocular disorders including vision changes, severe skin reactions, severe infusion site reactions, etc.)
    5. Padcev (enfortumab vedotin-ejfv) is considered medically necessary for adults patients for the following off-label uses:
        • Bladder Cancer
                • Used as subsequent-line systemic therapy (preferred) as a single agent for
                  • stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy or concurrent chemoradiotherapy
                  • stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with first-line systemic therapy or concurrent chemoradiotherapy
                  • stage IVA (any T, any N, M1a) disease if stable disease or progression following reassessment of tumor status after primary treatment with first-line systemic therapy
                  • stage IVB (any T, any N, M1b) disease
                  • muscle invasive local recurrence or persistent disease in a preserved bladder
                  • metastatic or local recurrence post cystectomy
        • Bladder Cancer - Upper GU Tract Tumors
                • Therapy for metastatic disease as a single agent for subsequent-line systemic therapy (preferred)
        • Bladder Cancer - Urothelial Carcinoma of the Prostate
                • Therapy for metastatic disease as a single agent for subsequent-line systemic therapy (preferred)
        • Bladder Cancer - Primary Carcinoma of the Urethra
                • Used as a single agent for recurrent or metastatic disease as subsequent-line systemic therapy (preferred) (*excluding 2B recommendation for recurrence of clinical stage T3-4 disease or palpable inguinal lymph nodes)

    6. Other uses of Padcev (enfortumab vedotin-ejfv) are considered investigational, including but not limited to, lung cancer and ovarian cancer.



Medicare Coverage:
There is no National Coverage Determination (NCD) for Enfortumab vedotin-ejfv (Padcev). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination specific to Padcev. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy. See generally, Local Coverage Article: Approved Drugs and Biologicals; Includes Cancer Chemotherapeutic Agents (A53049). Available at: https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=53049&ver=44&name=314*1&UpdatePeriod=711&bc=AQAAEAAAAAAAAA%3d%3d&.
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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:
Enfortumab vedotin-ejfv (Padcev)
Padcev (enfortumab vedotin-ejfv)

References:

1. Padcev (enfortumab vedotin-ejfv) [package insert]. Astellas Pharma US, Inc., Northbrook, Illinois. December 2019.

2. ClinicalTrials.gov. A Study of Enfortumab Vedotin for Patients with Locally Advanced or Metastatic Urothelial Bladder Cancer (EV-201). (NCT03219333.) Accessed December 30, 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT03219333?term=NCT03219333&draw=2&rank=1

3. Drug Trials Snapshot: PADCEV. Updated December 26, 2019. Accessed December 30, 2019. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-padcev?utm_campaign=PADCEV&utm_medium=email&utm_source=Eloqua

4. Padcev. National Comprehensive Cancer Network: Drugs and Biologics Compendium. Available at https://www.nccn.org/professionals/drug_compendium/content/. Accessed on 01/09/2020

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*

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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