Subject: Zelboraf 1685-A SGM P2023

Drug

ZELBORAF  (vemurafenib)

Policy:

      I.  INDICATIONS

          The indications below including FDA-approved indications and
          compendial uses are considered a covered benefit provided that
          all the approval criteria are met, and the member has no
          exclusions to the prescribed therapy.

          A.  FDA-Approved Indications
               1.  Zelboraf is indicated for the treatment of patients with
                    unresectable or metastatic melanoma with BRAF V600E
                    mutation as detected by an FDA-approved test.

                    Limitation of use: Zelboraf is not indicated for treatment
                    of patients with wild-type BRAF melanoma.
               2.  Zelboraf is indicated for the treatment of patients with
                    Erdheim-Chester Disease with BRAF V600 mutation.

          B.  Compendial Uses
               1.  Non-small cell lung cancer, BRAF V600E mutation-positive
               2.  Hairy cell leukemia
               3.  Thyroid carcinoma
                    a.  Papillary carcinoma
                    b.  Follicular carcinoma
                    c.  Hürthle cell carcinoma
               4.  Glioma, BRAF V600 activating mutation-positive
               5.  Meningioma, BRAF V600 activating mutation-positive
               6.  Astrocytoma, BRAF V600 activating mutation-positive
               7.  Cutaneous melanoma
               8.  Histiocytic Neoplasms
                    a.  Erdheim-Chester Disease
                    b.  Langerhans Cell Histiocytosis

          All other indications are considered experimental/investigational
          and not medically necessary.

    II.  DOCUMENTATION

          Submission of BRAF mutation documentation is necessary to
          initiate the prior authorization review for applicable indications
          as outlined in Section III.

  III.  CRITERIA FOR INITIAL APPROVAL

          A.  Cutaneous Melanoma
               Authorization of 12 months may be granted for treatment of
               cutaneous melanoma with a BRAF V600 activating mutation
               (e.g., V600E or V600K) in any of the following settings:
               1.  Unresectable or metastatic disease when used as a single
                    agent or in combination with cobimetinib (Cotellic) with
                    or without atezolizumab (Tecentriq).
               2.  Adjuvant treatment of resected stage III disease in
                    combination with cobimetinib (Cotellic) when the
                    member has had an unacceptable toxicity to dabrafenib
                    (Tafinlar) in combination with trametinib (Mekinist) or
                    dabrafenib/trametinib are less desirable based on side-
                    effect profiles.
               3.  Limited resectable local satellite/in-transit recurrent
                    disease in combination with cobimetinib (Cotellic) when
                    the member has had an unacceptable toxicity to
                    dabrafenib (Tafinlar) in combination with trametinib
                    (Mekinist) or dabrafenib/trametinib are less desirable
                    based on side-effect profiles.

          B.  Central Nervous System Cancer
               Authorization of 12 months may be granted for treatment of
               BRAF V600 mutation-positive (e.g., BRAF V600E or V600K
               mutation) gliomas, meningiomas, or astrocytomas.

          C.  Histiocytic Neoplasms
               Authorization of 12 months may be granted for treatment of
               BRAF V600 mutation-positive (e.g., BRAF V600E or V600K
               mutation) Erdheim-Chester disease or Langerhans cell
               histiocytosis as a single agent.

          D.  Non-small Cell Lung Cancer (NSCLC)
               Authorization of 12 months may be granted for treatment of
               BRAF V600E mutation-positive advanced or metastatic
               NSCLC, as a single agent, if the combination of dabrafenib
               (Tafinlar) plus trametinib (Mekinist) is not tolerated.

          E.  Hairy Cell Leukemia
               Authorization of 12 months may be granted for treatment of
               hairy cell leukemia for either of the following:
               1.  Subsequent therapy as a single agent or in combination
                    with rituximab, or
               2.  Initial therapy in combination with obinutuzumab for
                    members who are unable to tolerate purine analogs

          F.  Thyroid Carcinoma
               Authorization of 12 months may be granted when all of the
               following criteria are met:
               1.  Member has follicular, Hürthle cell, or papillary thyroid
                    carcinoma that is not amenable to radioactive iodine
                    (RAI) therapy.
               2.  Tumor is positive for BRAF mutation (e.g., BRAF V600E or
                    V600K).

   IV.  CONTINUATION OF THERAPY

          Authorization of 12 months may be granted for continued
          treatment in members requesting reauthorization for an
          indication listed in Section III when there is no evidence of
          unacceptable toxicity or disease progression while on the current
          regimen.

Place of Service:

Outpatient

The above policy is based on the following references:

1. Zelboraf [package insert]. South San Francisco, CA: Genentech USA, Inc.; May 2020.
2. The NCCN Drugs & Biologics Compendium 2021 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed November 5, 2021.
3. Usubalieva A, Pierson CR, Kavran CA, et al. Primary Meningeal Pleomorphic Xanthoastrocytoma With Anaplastic Features: A Report of 2 Cases, One With BRAFV600E Mutation and Clinical Response to the BRAF Inhibitor Dabrafenib. Journal of neuropathology and experimental neurology. 2015;74(10):960-969. doi:10.1097/NEN.0000000000000240.
4. Mordechai O, Postovsky S, Vlodavsky E, et al. Metastatic Rhabdoid Meningioma with BRAF V600E Mutation and Good Response to Personalized Therapy: Case Report and Review of the Literature. Pediatric Hematology and Oncology. 2015; 32:3, 207-211, DOI: 3109/08880018.2014.936058
5. Lassaletta, A, Guerreiro Stucklin, A, Ramaswamy, V, et al. Profound clinical and radiological response to BRAF inhibition in a 2‐month‐old diencephalic child with hypothalamic/chiasmatic glioma. Pediatric Blood and Cancer. 2016; 63: 2038-2041. doi:1002/pbc.26086.
6. Meletah SK, Pavlick D, Brennan T, et al. Personalized Treatment for a Patient with a BRAF V600E Mutation using Dabrafenib and a Tumor Treatment Fields Device in a High-Grade Glioma Arising from Ganglioglioma. Journal of the National Comprehensive Cancer Network. 2016; 14(11): 1345-1350.
7. National Comprehensive Cancer Network. Thyroid Carcinoma (Version 3.2022). Available at: https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. Accessed November 14, 2022.

 

 

 

 

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

May 15, 2023