CurrentUnitedHealthcarePolicy N/A

Afinitor (everolimus) prior authorization and coverage criteria

This policy governs prior authorization and coverage criteria for Afinitor (everolimus) for UnitedHealthcare members, specifying conditions, initial and reauthorization rules, and age-based provisions. It affects prescribers and pharmacy benefit administrators processing Afinitor prescriptions.

Policy Summary

PayerUnitedHealthcare

PolicyAfinitor (everolimus) prior authorization and coverage criteria

Policy CodePolicy N/A

Change TypeNo material changes — routine revision

Effective DateAug 1, 2025

Next Review DateMay 1, 2025

Key ActionSubmit prior authorization with diagnosis-specific documentation; approvals issued for 12 months when criteria are met.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 monthstypical authorization period

auto-processmembers <19 auto-process

no progressive diseasereauthorization requirement

2025 P 1003-14program number

Coverage Criteria for Afinitor (everolimus)

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Patients less than 19 years of age

Covered when ALL of the following are met for patients less than 19 years of age

Pediatric automatic approval: Patient is less than 19 years of age

Authorization will be issued for 12 months

Neuroendocrine Tumors - Initial Authorization

Initial authorization criteria for Neuroendocrine Tumors (NET)

NET indications: One of: (1) Both: diagnosis of neuroendocrine tumor of gastrointestinal, lung, or thymic origin AND disease that is unresectable, locally advanced, or metastatic; OR (2) Both: diagnosis of neuroendocrine tumor of pancreatic origin AND used for management of recurrent/locoregional advanced and/or metastatic disease or to stabilize glucose levels of locoregional insulinoma; OR (3) All: diagnosis of well-differentiated, grade 3 neuroendocrine tumor AND disease that is unresectable, locally advanced, or metastatic AND tumor has favorable biology (e.g., relatively low Ki-67 <55%, slow growing, positive SSTR-based PET imaging)Ki-67 <55% example

Authorization will be issued for 12 months

Neuroendocrine Tumors - Reauthorization

Reauthorization for Neuroendocrine Tumors

NET reauthorization: Patient does not show evidence of progressive disease while on Afinitor therapy

Authorization will be issued for 12 months

Kidney Cancer / TSC-associated RCC - Initial Authorization

Kidney cancer and TSC-associated renal cell carcinoma

Kidney cancer indications: Either: (1) Both: diagnosis of kidney cancer AND disease that is relapsed or stage IV; OR (2) Diagnosis of tuberous sclerosis complex (TSC)-associated renal cell carcinoma

Authorization will be issued for 12 months

Kidney Cancer - Reauthorization

Reauthorization for Kidney cancer

Kidney reauthorization: Patient does not show evidence of progressive disease while on Afinitor therapy

Authorization will be issued for 12 months

CNS Cancer - Initial Authorization

Central Nervous System cancers (SEGA, meningioma) initial authorization

CNS indications: Either: (1) Both: diagnosis of subependymal giant cell astrocytoma (SEGA) AND used as adjuvant treatment; OR (2) All: diagnosis of meningioma AND disease is recurrent or progressive AND surgery and/or radiation is not possible AND used in combination with bevacizumab or octreotide LAR

Authorization will be issued for 12 months

CNS Cancer - Reauthorization

Reauthorization for CNS cancers

CNS reauthorization: Patient does not show evidence of progressive disease while on Afinitor therapy

Authorization will be issued for 12 months

Waldenström's Macroglobulinemia / Lymphoplasmacytic Lymphoma

Waldenström's macroglobulinemia / Lymphoplasmacytic lymphoma

Waldenström's/LPL initial: Diagnosis of Waldenström's macroglobulinemia or lymphoplasmacytic lymphoma AND disease that is non-responsive to primary treatment, progressive, or relapsed

Authorization will be issued for 12 months

Waldenström's/LPL reauthorization: Patient does not show evidence of progressive disease while on Afinitor therapy

Authorization will be issued for 12 months

Breast Cancer - Initial and Reauthorization

Breast cancer (HR-positive, HER2-negative) initial authorization

Breast cancer initial: Diagnosis of recurrent or metastatic breast cancer AND disease that is hormone receptor (HR)-positive or inflammatory AND HER2-negative AND patient is postmenopausal OR (premenopausal and on ovarian ablation/suppression) OR male AND used in combination with exemestane (if progressed within 12 months or on a non-steroidal aromatase inhibitor), fulvestrant, or tamoxifenprogressed within 12 months on non-steroidal AI when exemestane used

Authorization will be issued for 12 months

Breast cancer reauthorization: Patient does not show evidence of progressive disease while on Afinitor therapy

Authorization will be issued for 12 months

HR-positive, HER2-negative advanced breast cancer (with endocrine therapy)

Covered when ALL of the following are met

Breast cancer criteria: (1) Disease is HR-positive (ER+ or PR+) OR breast cancer is inflammatory; (2) Disease is HER2-negative; (3) Patient is postmenopausal OR (patient is premenopausal AND on ovarian suppression) OR patient is male; (4) Used in combination with exemestane if progressed within 12 months or on a non-steroidal aromatase inhibitor, fulvestrant, or tamoxifen.

Classic Hodgkin lymphoma, relapsed/refractory

Covered when ALL of the following are met

Hodgkin lymphoma: (1) Diagnosis of classic Hodgkin lymphoma; (2) Disease is relapsed or refractory; (3) Patient is not a candidate for autologous stem cell rescue/high-dose therapy (ASCR/HDT).

Selected soft tissue sarcoma subtypes

Covered when ONE of the following subtypes is present

Soft tissue sarcoma subtypes: Locally advanced unresectable or metastatic PEComa; recurrent angiomyolipoma; lymphangioleiomyomatosis.

Thymic epithelial tumors

Covered when BOTH criteria are met

Thymoma/thymic carcinoma: (1) Diagnosis of thymic carcinoma or thymoma; (2) Used as first-line single-agent therapy for those who cannot tolerate combination regimens OR as second-line single-agent therapy.

Thyroid carcinoma (selected histologies)

Covered when ALL of the following are met

Thyroid carcinoma: (1) Diagnosis of follicular, oncocytic, or papillary carcinoma; (2) Unresectable locoregional recurrent, persistent, or metastatic disease; (3) Patient has symptomatic disease OR progressive disease.

Endometrial carcinoma and uterine sarcoma

Covered when ONE of the following is met

Endometrial/uterine indications: (1) Endometrial carcinoma used in combination with letrozole; OR (2) Uterine sarcoma that is PEComa used as second-line or subsequent therapy.

Tuberous sclerosis complex–associated partial-onset seizures

Covered when BOTH criteria are met

TSC seizures: (1) Diagnosis of tuberous sclerosis complex associated partial-onset seizures; (2) Used as adjunctive therapy.

Osteosarcoma (combination therapy)

Covered when ALL of the following are met

Osteosarcoma: (1) Diagnosis of osteosarcoma; (2) Disease is relapsed/refractory or metastatic; (3) Used as second-line therapy; (4) Used in combination with sorafenib (Nexavar).

Histiocytic disorders with PIK3CA mutation

Covered when BOTH criteria are met

Rosai-Dorfman, LCH, Erdheim-Chester: (1) Diagnosis of Rosai-Dorfman Disease, Langerhans Cell Histiocytosis, or Erdheim-Chester Disease; (2) Presence of PIK3CA mutation.

Initial Therapy — Histiocytic Neoplasms

Covered when ALL of the following are met

Histiocytic Neoplasms Initial Authorization: (1) Diagnosis of Rosai-Dorfman Disease OR Langerhans Cell Histiocytosis OR Erdheim-Chester Disease; AND (2) Presence of PIK3CA mutation

Authorization 12 months

Reauthorization

Reauthorization for Afinitor (all included indications)

Reauthorization: Patient does not show evidence of progressive disease while on Afinitor therapy

Authorization 12 months

Initial Therapy — Gastrointestinal Stromal Tumor (GIST)

Covered when ALL of the following are met

GIST Initial Authorization - diagnosis: (1) Diagnosis of Gastrointestinal Stromal Tumor (GIST)

GIST disease status: (2) Disease is one of: unresectable primary, recurrent/metastatic, gross residual (R2 resection), or tumor rupture

GIST prior therapy failure: (3) Disease has progressed after single-agent therapy with: (a) imatinib (Gleevec), (b) ripretinib (Qinlock), (c) regorafenib (Stivarga), (d) sunitinib (Sutent)

GIST combination use: (4) Afinitor is used in combination with one of: imatinib, regorafenib, or sunitinib

Authorization 12 months

Afinitor (everolimus) is not indicated for the treatment of patients with functional carcinoid tumors. This exclusion reflects the product labeling and is applied when assessing requests for coverage under this policy.

For all covered indications, reauthorization requires documentation that the patient does not show evidence of progressive disease while on Afinitor therapy. Requests that demonstrate disease progression during Afinitor treatment are not eligible for continued authorization.

Coverage decisions may be affected by external requirements: state mandates, federal regulatory requirements, member-specific benefit plan terms, other UnitedHealthcare policies, and utilization management programs can supersede or modify the criteria in this document. Additionally, UnitedHealthcare may use previous claims, medication history, diagnosis codes (ICD-10), and claim logic for automated approvals or reauthorizations, and supply limits may apply.

Provider Actions, Prior Authorization and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Afinitor (everolimus). Approvals are issued for 12 months when the specified initial criteria for the selected indication are met. Providers should confirm member-specific benefits and state mandates which may supersede these criteria.

Authorization duration: 12 months when initial criteria met
State mandates and federal regulatory requirements may apply and supersede policy language
Member-specific benefit plan coverage may impact approval

Documentation Required

Initial Authorization Requirements

Initial authorization requires documentation that supports the specific indication and all indication-specific clinical criteria listed below (diagnosis and any subtype/stage, disease status such as unresectable/locally advanced/metastatic/relapsed/recurrent/progressive, and combination therapy when required). Providers must submit relevant clinical history, prior therapies, and evidence of response or progression as applicable.

Include diagnosis with disease stage/subtype and clinical status (e.g., unresectable, locally advanced, metastatic, relapsed, recurrent, progressive)
Provide prior treatment history and dates, including specific agents when required by indication
Supply relevant testing (e.g., molecular testing) when required for the indication

Documentation Required

Initial Authorization — Histiocytic Neoplasms

For histiocytic neoplasms (Rosai-Dorfman Disease, Langerhans Cell Histiocytosis, Erdheim-Chester Disease), initial authorization requires documentation of the diagnosis and molecular testing demonstrating a PIK3CA mutation. Approvals are issued for 12 months.

Required diagnosis: Rosai-Dorfman Disease, Langerhans Cell Histiocytosis, or Erdheim-Chester Disease
Documentation required: PIK3CA mutation testing report
Authorization duration: 12 months

Step Therapy

Initial Authorization — GIST

For Gastrointestinal Stromal Tumor (GIST), initial authorization requires documentation of diagnosis, disease status (unresectable primary, recurrent/metastatic, gross residual/R2 resection, or tumor rupture), prior progression on all listed single-agent therapies, and use of Afinitor in combination with one of the specified agents. Approvals are issued for 12 months.

Required diagnosis: Gastrointestinal Stromal Tumor (GIST)
Required disease status: unresectable primary, recurrent/metastatic, gross residual (R2 resection), or tumor rupture
Prior therapy requirement: documentation of disease progression after single-agent therapy with imatinib (Gleevec), ripretinib (Qinlock), regorafenib (Stivarga), and sunitinib (Sutent)
Combination requirement: Afinitor must be used in combination with imatinib, regorafenib, or sunitinib
Authorization duration: 12 months

Denial Risk

Reauthorization Criteria and Denial Risk

Reauthorization for Afinitor (all included indications) requires documentation that the patient does not show evidence of progressive disease while on Afinitor therapy. Reauthorizations are issued for 12 months. Reauthorization will be denied if there is evidence of disease progression on therapy.

Reauthorization criterion: No evidence of progressive disease while on Afinitor
Denial trigger: Documented progressive disease during Afinitor therapy
Reauthorization duration: 12 months

Step Therapy

Combination Requirement for Breast Cancer

For HR-positive, HER2-negative breast cancer, Afinitor must be used in combination with specified endocrine therapies. Initial authorization requires documentation of hormone receptor status, HER2-negative status, disease recurrence or metastasis, menopausal status (or ovarian suppression when premenopausal), and the specific endocrine agent to be used in combination.

Indication requirements: HR-positive (ER+ or PR+) and HER2-negative breast cancer that is recurrent or metastatic
Patient eligibility: postmenopausal women, premenopausal women receiving ovarian ablation/suppression, or male patients
Combination therapy requirement: used in combination with exemestane (if progressed within 12 months or on a non-steroidal aromatase inhibitor), fulvestrant, or tamoxifen
Authorization duration: 12 months

Documentation Required

Combination Therapy Requirements

For certain indications, Afinitor is required to be used in combination with specific agents. Providers must document the concurrent agent and relevant prior therapies when combination or sequencing is required by the indication.

Examples: breast cancer (exemestane, fulvestrant, tamoxifen), endometrial carcinoma (letrozole), osteosarcoma (sorafenib), CNS meningioma (bevacizumab or octreotide LAR), and GIST (imatinib, regorafenib, or sunitinib)
Provide documentation of plan to use Afinitor with the specified concurrent agent

Note

State Mandates and Compendia

Some states mandate coverage for certain off-label uses or require use of specific compendia. Where state mandates or compendia requirements apply, they supersede the policy language. Providers should verify state-specific mandates and compendia applicability for the member.

State mandates and compendia may override policy criteria
Verify member's state-specific benefit mandates

Billing Rule

Use of Claims History for Authorization

UnitedHealthcare may use previous claim/medication history, ICD-10 diagnosis codes, and claim logic to approve initial authorizations or reauthorizations without additional documentation. Automated approval and re-approval processes vary by program and therapeutic class. Supply limits may apply.

Claims/medication history and ICD-10 codes may be used for automated approvals or reauthorizations
Automated processes vary by program/therapeutic class
Supply limits may be enforced

Initial Therapy and Authorization Duration

Initial Therapy

Initial authorization node examples by indication

Pediatric initial: Patient less than 19 years of age

Authorization will be issued for 12 months

NET initial: See Neuroendocrine Tumors - Initial Authorization

Authorization will be issued for 12 months

Breast cancer initial: See Breast Cancer - Initial Authorization

Authorization will be issued for 12 months

Initial Authorization Duration

Initial authorization is indication-specific and issued for 12 months when criteria are met.

See indication-specific initial criteria: Refer to the criteria sets for each diagnosis; authorization duration is 12 months if criteria are satisfied.

Initial therapy — Histiocytic neoplasms

Initial authorization criteria for histiocytic neoplasms

Initial — Histiocytic Neoplasms: Diagnosis of specified histiocytic neoplasm AND presence of PIK3CA mutation

Authorization 12 months

Initial therapy — GIST

Initial authorization criteria for GIST

Initial — GIST: Diagnosis of GIST; disease meets specified surgical/clinical criteria; progression after listed single-agent therapies; used in combination with specified agents

Authorization 12 months

Continuation and Reauthorization Criteria

Continuation Therapy

Reauthorization/continuation rules across indications

General continuation: For reauthorization, patient must not show evidence of progressive disease while on Afinitor therapy

Authorization will be issued for 12 months

Reauthorization

Reauthorization rules common across indications

Reauthorization criterion: Patient does not show evidence of progressive disease while on Afinitor therapy.

Continuation therapy / Reauthorization

Reauthorization rules

Continuation: Patient does not show evidence of progressive disease while on Afinitor therapy

Authorization 12 months

Step Therapy and Combination Requirements

Indication	Step therapy requirement
HR-positive, HER2-negative advanced or recurrent breast cancer
Afinitor must be used in combination with one of: exemestane (when patient progressed within 12 months or on a non-steroidal aromatase inhibitor), fulvestrant, or tamoxifen. Authorization issued for 12 months when criteria are met.

Indication	Combination requirement / Step therapy
Endometrial carcinoma
Afinitor must be used in combination with letrozole. Authorization issued for 12 months when criteria are met.
Uterine sarcoma (PEComa)
Used as second-line or subsequent therapy in PEComa; Afinitor used per indication (combination specified where noted). Authorization issued for 12 months when criteria are met.
Osteosarcoma (relapsed/refractory or metastatic)
Afinitor must be used in combination with sorafenib (Nexavar) as second-line therapy. Authorization issued for 12 months when criteria are met.

Indication	Step therapy / Combination requirement	Prior therapy failure requirement
Gastrointestinal Stromal Tumor (GIST) — unresectable primary, recurrent/metastatic, gross residual (R2), or tumor rupture
Afinitor must be used in combination with one of: imatinib (Gleevec), regorafenib (Stivarga), or sunitinib (Sutent). Authorization issued for 12 months when criteria are met.
Progression after single-agent therapy with imatinib, ripretinib (Qinlock), regorafenib, and sunitinib is required prior to Afinitor authorization

Definitions and Key Terms

SEGA — Definition

DefinitionSubependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex that requires therapeutic intervention but is not amenable to curative resection.

Typical age range noted in labelingAdult and pediatric patients aged 1 year and older may be treated for SEGA (per background indications).

Authorization noteAuthorization will be issued for 12 months when initial criteria are met.

PNET — Definition

DefinitionProgressive neuroendocrine tumors of pancreatic origin (PNET).

Related FDA indicationIndicated in adults with progressive neuroendocrine tumors of pancreatic origin.

Coverage contextAuthorization will be issued for 12 months when criteria are met.

HR-positive — Definition

DefinitionHormone receptor–positive (HR-positive) denotes estrogen-receptor-positive (ER+) or progesterone-receptor-positive (PR+).

Use in breast cancer criteriaHR-positive status is one required element for coverage of HR-positive, HER2-negative advanced breast cancer.

Combination therapy requirementWhen HR-positive, Afinitor must be used in combination with specified endocrine agents (exemestane, fulvestrant, or tamoxifen) per criteria.

PIK3CA mutation — Definition

DefinitionPIK3CA mutation: presence of a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation.

Indication relevanceA documented PIK3CA mutation is required for coverage of specified histiocytic disorders (Rosai-Dorfman disease, LCH, Erdheim-Chester Disease).

Authorization durationAuthorization for indications requiring PIK3CA mutation is issued for 12 months when criteria are met.

NCCN recognition — Definition

DefinitionNCCN recognition: the drug has been recognized for treatment of the cancer indication by the NCCN Drugs and Biologics Compendium with a Category of Evidence and Consensus of 1, 2A, or 2B.

Policy roleNCCN recognition is listed as supporting recommended regimens for multiple indications within the policy.

ExamplesNCCN lists indications including NET, breast cancer, kidney cancer, soft tissue sarcomas, GIST, histiocytic neoplasms, and others.

Background

Everolimus (Afinitor) is an mTOR kinase inhibitor with multiple FDA-approved oncology and tuberous sclerosis complex (TSC) indications, including HR‑positive, HER2‑negative advanced breast cancer (in combination with exemestane), progressive neuroendocrine tumors of pancreatic, gastrointestinal, or lung origin, advanced renal cell carcinoma after prior VEGF‑TKI therapy, renal angiomyolipoma in TSC, subependymal giant cell astrocytoma (SEGA) in TSC, and adjunctive therapy for TSC‑associated partial‑onset seizures. The drug is also recognized by NCCN for additional tumor types. UnitedHealthcare may apply program rules such as automated approval based on claims history and supply limits when implementing these coverage criteria.

Quantity Limits and Supply

Afinitor (everolimus) — Quantity limits

Supply limitsSupply limits may be in place for Afinitor (everolimus).

Automated approvalsUnitedHealthcare may approve initial and re-authorization based solely on previous claim/medication history, diagnosis codes (ICD-10), and/or claim logic; use of automated processes varies by program.

Unit/periodQuantity limits are referenced as 'per month' in the quantity limits module but specific numeric limits are unspecified in the policy text.

Policy Summary

PayerUnitedHealthcare

PolicyAfinitor (everolimus) prior authorization and coverage criteria

Policy CodePolicy N/A

Change TypeNo material changes — routine revision

Effective DateAug 1, 2025

Next Review DateMay 1, 2025

Key ActionSubmit prior authorization with diagnosis-specific documentation; approvals issued for 12 months when criteria are met.

SourceLink

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