Subject: Braftovi SGM 2616-A P2026

Drug

Braftovi

BRAFTOVI  (encorafenib)

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

·       Braftovi is indicated, in combination with binimetinib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.

·       Braftovi is indicated, in combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test.

·       Braftovi is indicated, in combination with cetuximab, for the treatment of adult patients with mCRC with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.

·       Braftovi is indicated, in combination with binimetinib, for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.

Limitations of Use

Braftovi is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC.

Compendial Uses^2-6

·       Cutaneous Melanoma

·       Central Nervous System Cancer

o   Glioma, BRAF V600 activating mutation-positive

o   Meningioma, BRAF V600 activating mutation-positive

o   Astrocytoma, BRAF V600 activating mutation-positive

·       Colorectal Cancer

·       Appendiceal Cancer

·       Non-Small Cell Lung Cancer

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.

Coverage Criteria

Cutaneous Melanoma^1,2

Authorization of 12 months may be granted for treatment of cutaneous melanoma with a BRAF V600 mutation positive (e.g., V600E or V600K mutations) cutaneous melanoma in any of the following settings:

·       Unresectable or metastatic disease when used either:

§  in combination with binimetinib (Mektovi), or

§  as a single agent, if BRAF/MEK inhibitor combination therapy is contraindicated

·       Neoadjuvant therapy of stage III disease in combination with binimetinib (Mektovi) 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 binimetinib (Mektovi) 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 binimetinib (Mektovi) 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^3-6

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

Colorectal Cancer^1,2,7,8

Authorization of 12 months may be granted for treatment of BRAF V600E mutation-positive colorectal cancer (including anal adenocarcinoma) when either of the following criteria are met:

·       The requested medication will be used in combination with either cetuximab (Erbitux) or panitumumab (Vectibix) and either of the following:

§  Will be used as subsequent therapy for advanced or metastatic disease

§  Will be used as primary treatment for unresectable metachronous metastases and the member has received FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months

·       The requested medication will be used in combination with FOLFOX regimen and either cetuximab (Erbitux) or panitumumab (Vectibix) for advanced, unresectable, medically inoperable, or metastatic disease.

Appendiceal Cancer²

Authorization of 12 months may be granted for treatment of BRAF V600E mutation-positive appendiceal neoplasms and cancers when one of the following criteria are met:

·       The requested medication will be used in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), with or without cetuximab (Erbitux) or panitumumab (Vectibux), for recurrent, progressive, or extraperitoneal disease

·       The requested medication will be used as neoadjuvant treatment in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) and cetuximab (Erbitux) or panitumumab (Vectibux) for recurrent or metastatic peritoneal-only disease

Non-Small Cell Lung Cancer (NSCLC)^1,2

Authorization of 12 months may be granted for treatment of BRAF V600E mutation-positive recurrent, advanced, or metastatic NSCLC in combination with binimetinib (Mektovi) when the member has not experienced disease progression on BRAF-targeted therapy.

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.        Braftovi [package insert]. Boulder, CO: Array BioPharma, Inc.; March 2025.

2.      The NCCN Drugs & Biologics Compendium® © 2025 National Comprehensive Cancer Network, Inc. Available at: https://www.nccn.org. Accessed November 10, 2025.

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: 10.3109/08880018.2014.936058

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:10.1002/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. NCCN Clinical Practice Guidelines in Oncology: Anal Carcinoma. Version 5.2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf. Accessed November 10, 2025.

8.      National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Version 5.2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf Accessed November 10, 2025.

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 18, 2026