Subject: Zelboraf 1685-A SGM P2024a
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, papillary
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 BRAF V600 mutation-positive
(e.g., BRAF V600E or V600K mutations) cutaneous melanoma in any of the following
settings:
1. Unresectable or metastatic disease when used either:
i. as a single agent, if BRAF/MEK inhibitor combination therapy is contraindicated
ii. in combination with cobimetinib (Cotellic) with or without atezolizumab (Tecentriq)
2. Neoadjuvant therapy in combination with cobimetinib (Cotellic) if immunotherapy is
contraindicated 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. 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.
4. 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, recurrent, or metastatic NSCLC, as a single agent, if the combination of
dabrafenib (Tafinlar) plus trametinib (Mekinist) is not tolerated and the member has not
experienced disease progression on BRAF-targeted therapy.
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 recurrent or metastatic papillary thyroid carcinoma that is refractory to
radioactive iodine (RAI) therapy.
2. Tumor is positive for BRAF V600E.
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:
- Zelboraf [package insert]. South San Francisco, CA: Genentech USA, Inc.; May 2020.
- The NCCN Drugs & Biologics Compendium® © 2024 National Comprehensive Cancer Network, Inc. Available at: https://www.nccn.org. Accessed April 30, 2024.
- 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.
- 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
- 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.
- 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.
- Lexicomp [database online]. Hudson, OH: Lexi-Comp, Inc. Available at: https://online.lexi.com/lco/action/home [available with subscription]. Accessed November 13, 2023.
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.
June 08, 2024
