Subject: Mekinist 1681-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. Mekinist is indicated, as a single agent in BRAF-inhibitor treatment-naïve patients or in
combination with dabrafenib, for the treatment of patients with unresectable or metastatic
melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.
2. Mekinist is indicated, in combination with dabrafenib, for the adjuvant treatment of
patients with melanoma with BRAF V600E or V600K mutations as detected by an FDA-
approved test, and involvement of lymph node(s), following complete resection.
3. Mekinist is indicated, in combination with dabrafenib, for the treatment of patients with
metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected
by an FDA-approved test.
4. Mekinist is indicated, in combination with dabrafenib, for the treatment of patients with
locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E
mutation and no satisfactory locoregional treatment options.
5. Mekinist is indicated, in combination with dabrafenib, for the treatment of adult and
pediatric patients 1 year of age and older with unresectable or metastatic solid tumors
with BRAF V600E mutation who have progressed following prior treatment and have no
satisfactory alternative treatment options.
6. Mekinist is indicated, in combination with dabrafenib, for the treatment of pediatric
patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E
mutation who require systemic therapy.
Limitations of Use: Mekinist is not indicated for treatment of patients with colorectal cancer
because of known intrinsic resistance to BRAF inhibition.
B. Compendial Uses
1. Melanoma (including brain metastases), BRAF V600 activating mutation-positive
2. Glioma, BRAF V600 activating mutation-positive
3. Meningioma, BRAF V600 activating mutation-positive
4. Astrocytoma, BRAF V600 activating mutation-positive
5. Uveal melanoma as a single agent
6. Brain cancer and neurofibromatosis type 1
7. Non-small cell lung cancer (NSCLC)
8. Ovarian cancer/fallopian tube cancer/primary peritoneal cancer
9. Biliary tract cancers
i. Gallbladder cancer
ii. Extrahepatic cholangiocarcinoma
iii. Intrahepatic cholangiocarcinoma
10. Histiocytic neoplasms
i. Erdheim-Chester disease
ii. Langerhans cell histiocytosis
iii. Rosai-Dorfman disease
11. Anaplastic thyroid carcinoma
12. Gastrointestinal stromal tumor
13. Pancreatic adenocarcinoma
14. Salivary gland tumor
15. Gastric adenocarcinoma
16. Esophageal and esophageal junction cancer
17. Hairy cell leukemia
18. Small bowel adenocarcinoma
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. Melanoma
Authorization of 12 months may be granted for treatment of melanoma in any of the
following settings:
1. Unresectable or metastatic cutaneous melanoma when used either:
i. as single agent subsequent therapy for disease that is BRAF gene fusion- and non-
V600 mutation-positive, or
ii. in combination with dabrafenib (Tafinlar) with or without pembrolizumab (Keytruda)
for disease with a BRAF V600 activating mutation (e.g., V600E or V600K)
2. Brain metastases from melanoma with a BRAF V600E activating mutation in
combination with dabrafenib (Tafinlar).
3. Neoadjuvant treatment of BRAF V600 mutation-positive cutaneous melanoma in
combination with dabrafenib (Tafinlar) if immunotherapy is contraindicated.
4. Adjuvant treatment of resected stage III cutaneous melanoma with a BRAF V600
activating mutation in combination with dabrafenib (Tafinlar).
5. Limited resectable local satellite/in-transit recurrent disease with a BRAF V600 activating
mutation in combination with dabrafenib (Tafinlar).
6. Uveal melanoma as a single agent for metastatic or unresectable disease.
B. Non-Small Cell Lung Cancer (NSCLC)
Authorization of 12 months may be granted for treatment of BRAF V600E mutation-positive
recurrent, advanced, or metastatic NSCLC in combination with dabrafenib (Tafinlar) when
the member has not experienced disease progression on BRAF-targeted therapy.
C. Anaplastic Thyroid Cancer
Authorization of 12 months may be granted for treatment of BRAF V600E mutation-positive
locally advanced or stage IV anaplastic thyroid carcinoma in combination with dabrafenib
(Tafinlar).
D. Central Nervous System Cancer
Authorization of 12 months may be granted for treatment of central nervous system cancer
in a member with either of the following:
1. BRAF V600 mutation-positive gliomas, meningiomas, or astrocytomas
2. Brain cancer and neurofibromatosis type 1
E. Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer
Authorization of 12 months may be granted for treatment of persistent or recurrent epithelial
ovarian cancer, fallopian tube cancer, primary peritoneal cancer, carcinosarcoma (malignant
mixed Mullerian tumors), clear cell carcinoma of the ovary, grade 1 endometrioid carcinoma,
low-grade serous ovarian carcinoma/ ovarian borderline epithelial tumors (low malignant
potential) or mucinous carcinoma of the ovary.
F. Biliary Tract Cancers
Authorization of 12 months may be granted for subsequent treatment of progressive BRAF-
V600E mutation-positive unresectable, resected gross residual (R2), or metastatic
gallbladder cancer, extrahepatic cholangiocarcinoma, or intrahepatic cholangiocarcinoma in
combination with dabrafenib (Tafinlar).
G. Histiocytic Neoplasms
Authorization of 12 months may be granted for treatment of Erdheim-Chester disease,
Langerhans cell histiocytosis, or Rosai-Dorfman disease as a single agent.
H. Solid Tumors
Authorization of 12 months may be granted for treatment of unresectable or metastatic solid
tumors when all of the following criteria are met:
1. The tumors are BRAF V600E mutation positive.
2. The disease has progressed following prior treatment and there are no satisfactory
alternative treatment options.
3. The member is 1 year of age or older.
4. The requested medication will not be used for the treatment of colorectal cancer.
5. The requested medication will be used in combination with dabrafenib (Tafinlar).
I. Gastrointestinal Stromal Tumor (GIST)
Authorization of 12 months may be granted for treatment of BRAF V600E mutation-positive
GIST in combination with dabrafenib (Tafinlar) when used as either of the following:
1. Neoadjuvant therapy
2. First-line therapy for gross residual disease (R2 resection), unresectable primary
disease, tumor rupture or recurrent/metastatic disease
J. Pancreatic Adenocarcinoma
Authorization of 12 months may be granted for treatment of BRAF V600E mutation-positive
recurrent, locally advanced, or metastatic disease in combination with dabrafenib (Tafinlar).
K. Salivary Gland Tumors
Authorization of 12 months may be granted for treatment of BRAF V600E mutation-positive
recurrent salivary gland tumor in combination with dabrafenib (Tafinlar).
L. Gastric, Esophageal and Esophagogastric Junction Cancer
Authorization of 12 months may be granted for subsequent treatment of BRAF V600E
mutation-positive unresectable locally advanced, recurrent, or metastatic disease or for
members who are not surgical candidates, in combination with dabrafenib (Tafinlar).
M. Hairy Cell Leukemia
Authorization of 12 months may be granted for treatment of relapsed/refractory hairy cell
leukemia in combination with dabrafenib (Tafinlar) if not previously treated with BRAF
inhibitor therapy.
N. Small Bowel Adenocarcinoma
Authorization of 12 months may be granted for treatment of BRAF V600E mutation-positive
advanced or metastatic small bowel adenocarcinoma in combination with dabrafenib
(Tafinlar).
IV. CONTINUATION OF THERAPY
Authorization of 12 months may be granted for continuation of therapy for an indication outlined
in section III when there is no evidence of unacceptable toxicity or disease progression or
recurrence while on the current regimen. For patients using Mekinist for adjuvant treatment of
cutaneous melanoma, only 12 months of therapy total will be approved.
Place of Service:
Outpatient
The above policy is based on the following references:
- Mekinist [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corporation; August 2023.
- 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 BRAFV600EMutation and Clinical Response to the BRAF Inhibitor Dabrafenib. J Neuropathol Exp Neurol. 2015;74(10):960-969. doi:10.1097/NEN.0000000000000240.
- Mordechai O, Postovsky S, Vlodavsky E, et al.Metastatic Rhabdoid Meningioma with BRAFV600E Mutation and Good Response to Personalized Therapy: Case Report and Review of the Literature. Pediatr Hematol Oncol. 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.
- Meletath 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. J Natl Compr Canc Netw. 2016;14(11):1345-1350.
- Knight T, Shatara M, Carvalho L, et al. Dramatic response to trametinib in a male child with neurofibromatosis type 1 and refractory astrocytoma. Pediatr Blood Cancer. 2019; 66(1):e27474.
- See WL, Tan IL, Mukherjee J, et al. Sensitivity of Glioblastomas to Clinically Available MEK Inhibitors Is Defined by Neurofibromin 1 Deficiency. Cancer Res. 2012;72(13):3350.
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
