Subject: Zelboraf SGM 1685-A P2025

Drug

ZELBORAF  (vemurafenib)

Policy:

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.

FDA-approved Indications¹

• Zelboraf is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.
• Zelboraf is indicated for the treatment of patients with Erdheim-Chester Disease with BRAF V600 mutation.

Limitation of use

Zelboraf is not indicated for treatment of patients with wild-type BRAF melanoma.

Compendial Uses^2-9

• Non-small cell lung cancer, BRAF V600E mutation-positive
• Hairy cell leukemia
• Thyroid carcinoma, papillary
• Glioma, BRAF V600 activating mutation-positive
• Meningioma, BRAF V600 activating mutation-positive
• Astrocytoma, BRAF V600 activating mutation-positive
• Cutaneous melanoma
• Histiocytic Neoplasms
  • Erdheim-Chester Disease
  • Langerhans Cell Histiocytosis

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

Documentation

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

Coverage Criteria

Cutaneous Melanoma^1-4

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:

• Unresectable or metastatic disease when used either:
  • as a single agent, if BRAF/MEK inhibitor combination therapy is contraindicated
  • in combination with cobimetinib (Cotellic) with or without atezolizumab (Tecentriq) or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza)
• 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.
• 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.
• 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.

Central Nervous System Cancer^2,5-8

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.

Histiocytic Neoplasms^1,2

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.

Non-small Cell Lung Cancer (NSCLC)²

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.

Hairy Cell Leukemia²

Authorization of 12 months may be granted for treatment of hairy cell leukemia for either of the following:

• Subsequent therapy as a single agent or in combination with rituximab, or
• Initial therapy in combination with obinutuzumab or rituximab for members who are unable to tolerate purine analogs

Thyroid Carcinoma⁹

Authorization of 12 months may be granted when all of the following criteria are met:

• Member has recurrent or metastatic papillary thyroid carcinoma that is refractory to radioactive iodine (RAI) therapy.
• Tumor is positive for BRAF V600E.

Continuation of Therapy

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization for an indication listed in the coverage criteria section 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® © 2024 National Comprehensive Cancer Network, Inc. Available at: https://www.nccn.org. Accessed November 8, 2024.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 3.2024. https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Accessed November 8, 2024.
4. Tecentriq Hybreza [package insert]. South San Francisco, CA: Genentech, Inc.; September 2024.
5. 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.
6. 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: 10.3109/08880018.2014.936058.
7. 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:10.1002/pbc.26086.
8. 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.
9. Lexi-Drugs. UpToDate Lexidrug. UpToDate Inc. https://online.lexi.com. Accessed November 8, 2024.

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.

April 18, 2025