Subject: everolimus products SGM 2021-A P2025

Drug

AFINITOR  (everolimus)

AFINITOR DISPERZ  (everolimus)

TORPENZ  (everolimus)

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 Indications^1-4

Hormone Receptor-Positive, HER2-Negative Breast Cancer

Afinitor and Torpenz are indicated for the treatment of postmenopausal women with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in combination with exemestane, after failure of treatment with letrozole or anastrozole.

Neuroendocrine Tumors (NET)

• Afinitor is indicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease.
• Afinitor is indicated for the treatment of adult patients with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin with unresectable, locally advanced or metastatic disease.

Renal Cell Carcinoma (RCC)

Afinitor is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.

Tuberous Sclerosis Complex (TSC)-Associated Renal Angiomyolipoma

Afinitor and Torpenz are indicated for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.

Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA)

Afinitor, Afinitor Disperz, and Torpenz are indicated in adult and pediatric patients aged 1 year and older with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.

Tuberous Sclerosis Complex (TSC)-Associated Partial-Onset Seizures

Afinitor Disperz is indicated for the adjunctive treatment of adult and pediatric patients aged 2 years and older with TSC-associated partial-onset seizures.

Compendial Uses^5-13

• Relapsed or stage IV renal cell carcinoma
• Soft tissue sarcoma subtypes:
  • Perivascular epithelioid cell tumors (PEComa)
  • Angiomyolipoma
  • Lymphangioleiomyomatosis
• Gastrointestinal stromal tumors (GIST)
• Neuroendocrine tumors:
  • Neuroendocrine tumors of the gastrointestinal tract, lung and thymus (carcinoid tumors)
  • Neuroendocrine tumors of the pancreas
  • Well differentiated Grade 3 neuroendocrine tumors
• Thymomas and thymic carcinomas
• Classic Hodgkin lymphoma
• Central nervous system cancers:
  • Meningiomas
  • Glioma
  • Subependymal giant cell astrocytoma (SEGA)
• Thyroid carcinoma (papillary carcinoma, oncocytic/Hürthle cell carcinoma, and follicular carcinoma)
• Waldenström macroglobulinemia/lymphoplasmacytic lymphoma
• Uterine Neoplasms (uterine sarcoma, endometrial carcinoma)
• HR+/HER2- breast cancer, recurrent unresectable or stage IV (M1)
• Tuberous sclerosis complex
• Histiocytic Neoplasms:
  • Erdheim-Chester Disease (ECD)
  • Langerhans Cell Histiocytosis (LCH)
  • Rosai-Dorfman Disease

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

Documentation

Submission of the following information is necessary to initiate the prior authorization review:

• Documentation of the presence of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation (where applicable)
• Hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (where applicable)

Coverage Criteria

Breast Cancer^1-7

Authorization of 12 months may be granted for subsequent treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative recurrent unresectable, advanced, or metastatic breast cancer when prescribed in combination with exemestane, fulvestrant, or tamoxifen.

Renal Cell Carcinoma^1-5

Authorization of 12 months may be granted for treatment of relapsed, advanced, or stage IV renal cell carcinoma when any of the following criteria are met:

• The requested medication is given as a single agent or in combination with lenvatinib as subsequent therapy for clear cell histology; OR
• The requested medication is given as single-agent or in combination with lenvatinib or bevacizumab for non-clear cell histology.

Neuroendocrine Tumors^1-5

Authorization of 12 months may be granted for the treatment of the following neuroendocrine tumors:

• Neuroendocrine tumors of the gastrointestinal tract, lung, and thymus (carcinoid tumors)
• Neuroendocrine tumors of the pancreas
• Well differentiated Grade 3 neuroendocrine tumors

Tuberous Sclerosis Complex (TSC)^1-4,8,10

Authorization of 12 months may be granted for treatment of TSC.

Soft Tissue Sarcoma⁵

Authorization of 12 months may be granted for treatment of any of the following subtypes of soft tissue sarcoma as single agent therapy: locally advanced unresectable or metastatic perivascular epithelioid cell tumor (PEComa), recurrent angiomyolipoma, or recurrent lymphangioleiomyomatosis.

Gastrointestinal Stromal Tumor (GIST)⁵

Authorization of 12 months may be granted for treatment of residual, unresectable, recurrent, metastatic, ortumor rupture GIST in combination with either imatinib, sunitinib, or regorafenib for members who have failed at least four FDA-approved therapies (e.g., imatinib, sunitinib, regorafenib, ripretinib).

Thymoma and Thymic Carcinoma⁵

Authorization of 12 months may be granted for treatment of thymoma or thymic carcinoma as a single agent.

Classic Hodgkin Lymphoma^5,9

Authorization of 12 months may be granted for subsequent treatment of relapsed or refractory classic Hodgkin lymphoma, as a single agent.

Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma⁵

Authorization of 12 months may be granted for treatment of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma as a single-agent therapy for previously treated disease.

Papillary or Follicular Thyroid Carcinoma⁵

Authorization of 12 months may be granted for treatment of progressive and/or symptomatic papillaryor follicular thyroid carcinoma not amenable to radioactive iodine (RAI) therapy.

Oncocytic Thyroid Carcinoma⁵

Authorization of 12 months may be granted for treatment of progressive and/or symptomatic oncocytic/Hürthle cell thyroid carcinoma.

Uterine Neoplasms⁵

Authorization of 12 months may be granted for treatment of the following uterine neoplasms:

• Endometrial carcinoma in combination with letrozole
• Uterine sarcoma as a single agent for subsequent therapy

Central Nervous System Cancers^5,11-13

Authorization of 12 months may be granted for treatment of the following central nervous system cancers:

• Glioma (including glioblastoma) or meningioma
• Adjuvant treatment of subependymal giant cell astrocytoma (SEGA) as a single agent

Histiocytic Neoplasms⁵

Authorization of 12 months may be granted for the treatment of any of the following histiocytic neoplasm subtypes as a single agent in members with a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation:

• Symptomatic or relapsed/refractory Erdheim-Chester Disease (ECD)
• Symptomatic or relapsed/refractory Rosai-Dorfman Disease
• Langerhans Cell Histiocytosis (LCH)

Continuation of Therapy

Authorization of 12 months may be granted for continued treatment in members requesting reauthorization for an indication in the coverage criteria 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. Afinitor and Afinitor Disperz [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; February 2022.
2. Torpenz [package insert]. Maple Grove, MN: Upsher-Smith Laboratories, LLC; June 2024.
3. Everolimus [package insert]. Iselin, NJ: Biocon Pharma Inc.; March 2025.
4. Everolimus tablet for suspension [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; May 2023.
5. The NCCN Drugs & Biologics Compendium 2025 National Comprehensive Cancer Network, Inc. https://www.nccn.org. Accessed May 7, 2025.
6. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N Engl J Med. 2012;366(6):520-529.
7. Yardley DA, Noguchi S, Pritchard KI, et al. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther 2013;30:870-884.
8. Sampson JR. Therapeutic targeting of mTOR in tuberous sclerosis. Biochem Soc Trans. 2009;37:259-264.
9. Johnston PB, Inwards DJ, Colgan JP, et al. A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol 2010;85:320-324.
10. Darcy A. Krueger, Hope Northrup, et al. Tuberous Sclerosis Complex Surveillance and Management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatric Neurology. 2013. 49: 255-265.
11. Wahl Michael, Chang, Susan, et al. Probing the PI3K/mTOR Pathway in Gliomas: A Phase II Study of Everolimus for Recurrent Adult Low Grade Gliomas. Cancer. 2017; 123 (23): 4631-4639.
12. Shih KC, Chowdhary S, et al. A Phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive, intracranial meningioma. Journal of Neuro-Oncology. 2016. 129 (2): 281-8.
13. Hainsworth, John D, et al. Phase II Study of concurrent radiation therapy, temozolomide, and bevacizumab followed by bevacizumab/everolimus as first-line treatment of patients with glioblastoma. Clin adv Hematol. Oncol. 2012. 10 (4): 240-6.

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.

October 12, 2025