Centene everolimus Coverage Prior Auth Policy

Coverage Criteria — Indication-specific Rules

Initial Therapy — Breast Cancer

Covered when ALL of the following are met

Breast Cancer initial criteria: 1) Request is for Afinitor or Afinitor Disperz; 2) Diagnosis of recurrent or metastatic breast cancer; 3) Prescribed by or in consultation with an oncologist; 4) Age >= 18 years; 5) Disease is hormone receptor (HR)-positive and HER2-negative; 6) Member must use generic everolimus, if available, unless contraindicated or intolerant; 7) History of endocrine therapy unless contraindicated or intolerant; 8) Prescribed in combination with exemestane, fulvestrant, or tamoxifen; 9) Dose does not exceed listed limits (Afinitor 2 tablets/day; Afinitor Disperz 4 tablets/day; maximum 20 mg/day) or is supported by practice guidelines/peer-reviewed literature with documentationdose limits: Afinitor 2 tabs/day; Afinitor Disperz 4 tabs/day; max 20 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN where applicable.

Initial Therapy — Neuroendocrine Tumors

Covered when ALL of the following are met

Neuroendocrine Tumor initial criteria: 1) Request is for Afinitor or Afinitor Disperz; 2) Tumor origin: pancreatic, gastrointestinal tract, lung, or thymus (thymus considered off-label); 3) Disease is unresectable, locally advanced, or metastatic; 4) Prescribed by or in consultation with an oncologist; 5) Age >= 18 years; 6) Member must use generic everolimus, if available, unless contraindicated or intolerant; 7) Dose does not exceed listed limits (Afinitor 2 tablets/day; Afinitor Disperz 4 tablets/day; maximum 20 mg/day) or is supported by practice guidelines/peer-reviewed literature with documentationdose limits: Afinitor 2 tabs/day; Afinitor Disperz 4 tabs/day; max 20 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy — Renal Cell Carcinoma

Covered when ALL of the following are met

RCC initial criteria: 1) Request is for Afinitor or Afinitor Disperz; 2) Diagnosis of relapsed or stage IV (unresectable or metastatic) renal cell carcinoma; 3) Prescribed by or in consultation with an oncologist; 4) Age >= 18 years; 5) Member must use generic everolimus, if available, unless contraindicated or intolerant; 6) If clear cell histology, prior failure of a therapy (see Appendix B) unless contraindicated or intolerant; 7) Dose does not exceed listed limits (Afinitor 2 tablets/day; Afinitor Disperz 4 tablets/day; maximum 20 mg/day) or is supported by practice guidelines/peer-reviewed literature with documentationdose limits: Afinitor 2 tabs/day; Afinitor Disperz 4 tabs/day; max 20 mg/day

Prior authorization may require documentation of prior therapies.

Initial Therapy — Renal Angiomyolipoma with TSC

Covered when ALL of the following are met

Renal AML with TSC initial criteria: 1) Request is for Afinitor or Afinitor Disperz; 2) Diagnosis of renal angiomyolipoma associated with tuberous sclerosis complex not requiring immediate surgery; 3) Prescribed by or in consultation with an oncologist; 4) Age > 18 years; 5) Member must use generic everolimus, if available, unless contraindicated or intolerant; 6) Dose does not exceed listed limits (Afinitor 2 tablets/day; Afinitor Disperz 4 tablets/day; maximum 20 mg/day) or is supported by practice guidelines/peer-reviewed literature with documentationdose limits: Afinitor 2 tabs/day; Afinitor Disperz 4 tabs/day; max 20 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy — TSC with SEGA

Covered when ALL of the following are met

TSC-SEGA initial criteria: 1) Request is for Afinitor or Afinitor Disperz; 2) Diagnosis of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex; 3) Prescribed by or in consultation with an oncologist; 4) Age >= 1 year; 5) Member must use generic everolimus, if available, unless contraindicated or intolerant

Prescribed regimen must be FDA-approved or recommended by NCCN where applicable.

Initial Therapy — TSC-associated Seizures (Adjunctive)

Covered when ALL of the following are met

TSC-associated seizures initial criteria: 1) Request is for Afinitor Disperz; 2) Diagnosis of partial-onset seizures associated with tuberous sclerosis complex; 3) Prescribed by or in consultation with an oncologist or neurologist; 4) Afinitor Disperz used as adjunctive therapy; 5) Age >= 2 years; 6) Member must use generic everolimus, if available, unless contraindicated or intolerant

HIM line of business refers to HIM.PA.103 for Afinitor Disperz.

Initial Therapy — Organ Rejection Prophylaxis (Zortress)

Covered when ALL of the following are met

Organ rejection prophylaxis initial criteria: 1) Member has received or is scheduled for a kidney or liver transplant; 2) Request is for Zortress; 3) Prescribed by or in consultation with a nephrologist, hepatologist, or transplant specialist; 4) Age > 18 years; 5) For kidney transplant: prior failure of tacrolimus unless contraindicated or intolerant; 6) For kidney transplant use: combination with Simulect, cyclosporine (reduced doses), and corticosteroids as specified; 7) For liver transplant use: combination with tacrolimus (reduced doses) and corticosteroids as specified; 8) Member must use generic everolimus, if available, unless contraindicated or intolerant

Safety/efficacy limitations noted for non-kidney/liver organ recipients and pediatric patients for Zortress.

inv-08: Organ rejection prophylaxis (Zortress)

Covered when ALL of the following are met:

Transplant prophylaxis requirements: Member has received or is scheduled for a kidney or liver transplant; request is for Zortress; prescribed by or in consultation with a nephrologist, hepatologist, or transplant specialist; age > 18 years; for kidney transplant, failure of tacrolimus unless contraindicated or adverse effects; Zortress to be used as generic everolimus if available unless contraindicated; prescribed in combination with specified agents (e.g., for kidney: Simulect, cyclosporine, corticosteroids; for liver: tacrolimus and corticosteroids)

From section G: Prophylaxis of Organ Rejection.

NCCN-based oncology indications (Afinitor/Afinitor Disperz)

Covered when ALL of the following are met:

Product and diagnosis: 1) Request is for Afinitor or Afinitor Disperz; 2) Diagnosis is one of the listed tumor types per NCCN Compendium (examples include Hodgkin lymphoma, WM/indolent lymphoproliferative disorders, thymoma/thymic carcinoma, PEComa, recurrent angiomyolipoma, lymphangioleiomyomatosis, endometrial carcinoma in combination with letrozole, histiocytic neoplasms, GIST in combination with listed agents for progression after prior therapies, osteosarcoma with sorafenib or similar, differentiated thyroid cancer, meningiomas with bevacizumab or octreotide LAR)

NCCN Compendium indications (off-label) list; prescribed regimen must be FDA-approved or recommended by NCCN.

Prescriber and dosing: Prescribed by or in consultation with an oncologist; dose is within FDA maximum limit for any FDA-approved indication (or supported by practice guidelines/peer-reviewed literature for relevant off-label use) — prescriber must submit supporting evidence if off-label

From NCCN Compendium Indications section.

Use of generic: For Afinitor or Afinitor Disperz requests, member must use generic everolimus if available unless contraindicated or clinically significant adverse effects are experienced

Continuation Therapy

Covered when ALL of the following are met for continued therapy:

Current therapy and benefit: Member is currently receiving the medication via Centene benefit with documentation that the member has been on Afinitor, Afinitor Disperz, or Zortress for at least 30 days and is responding positively to therapy

Continuation criteria

Dose increase limits: For all indications except partial-onset seizures (TSC), SEGA (TSC), and organ rejection prophylaxis, if request is for a dose increase the new dose must not exceed 20 mg/day, Afinitor 2 tablets/day, Afinitor Disperz 4 tablets/day, or be supported by guidelines/peer-reviewed literature with documentationdose limits: Afinitor 2 tabs/day; Afinitor Disperz 4 tabs/day; max 20 mg/day

Dose limits for continuation

Generic use: Member must use generic everolimus if available unless contraindicated or clinically significant adverse effects are experienced

Continuation generic-first

Other/Unlisted Indications

When requested indication is not specifically listed:

Formulary and policy cross-reference: If drug is on the formulary/PDL for the relevant line of business, follow the no coverage criteria policy for that line (CP.CPA.190 commercial, HIM.PA.33 marketplace, CP PMN.255 Medicaid); if not on the formulary/PDL, follow the non-formulary policy for the relevant line (CP.CPA.190 commercial, HIM.PA.103 marketplace, CP PMN.16 Medicaid)

Cross-reference guidance

Off-label pathway: If the requested use is not listed and criterion above does not apply, refer to the off-label use policy for the relevant line of business (CP.CPA.09 commercial, HIM.PA.154 marketplace, CPPMN.53 Medicaid)

Alternate pathway for unlisted uses

Coverage for Afinitor excludes certain labeled limitations: specifically, Afinitor is not indicated for treatment of patients with functional carcinoid tumors. For Zortress, safety and efficacy have not been established for recipients of transplanted organs other than kidney or liver, for kidney transplant patients at high immunologic risk, and for pediatric patients (<18 years).

Requests for non‑FDA approved indications that are not addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (for example, CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, and CPPMN.53 for Medicaid).

When state Medicaid coverage provisions conflict with this clinical policy, state Medicaid coverage provisions take precedence. Providers and reviewers should follow the applicable state Medicaid manual for any differing coverage requirements.

Initial Therapy — Per-Indication Requirements

Initial therapy rules

Initial therapy requirements by indication

See indication-specific initial criteria: See coverage.criteria_sets for detailed, indication-specific initial authorization criteria including prescriber specialty, prior therapy requirements, age limits, generic-use preference, and dose limits.

Initial Therapy — operational initial authorization requirements (summary block)

Initial authorization requirements

Product and prescriber: Request for specific product (Afinitor/Afinitor Disperz or Zortress) with appropriate specialist prescriber/consultation (oncologist for Afinitor; nephrologist/hepatologist/transplant specialist for Zortress)

Initial prescriber requirement

Generic-first:

Continuation / Renewal Criteria and Durations

Continuation/Approval Duration

Approval durations by line of business

Approval duration rules: Commercial: up to 12 months or duration of request, whichever is less; Medicaid: 6 months; HIM: 6 months (refer to HIM.PA.103 for Afinitor Disperz)

Duration may vary by indication as specified in each section.

Continuation Therapy (drug-specific)

Continuation therapy requirements

Active therapy and benefit: Member currently receiving via Centene benefit and has been on drug for ≥30 days with documentation of positive response

From Continued Therapy section

Dose increase constraints:

Provider Requirements and Authorization Workflow

Prior Authorization

Prior Authorization Required

Prior authorization is required for Afinitor (everolimus), Afinitor Disperz, and Zortress (everolimus) for all indications described in this policy. Provider must submit a prior authorization request and include sufficient clinical documentation to demonstrate that the member meets the applicable approval criteria for the requested indication.

Affected products: Afinitor, Afinitor Disperz, Zortress (everolimus formulations).
Requests must clearly identify the requested product, indication, dose, and regimen.
Submit supporting clinical documentation (office notes, pathology reports, imaging, lab results, operative reports, prior therapy history).

Prior Authorization

Prior Authorization and Approval Durations

Authorizations historically have been issued for durations aligned with line of business and the indication. Typical approval lengths in this policy have included: Medicaid — 6 months; HIM/legacy lines — 6 months (see HIM.PA.103 for Afinitor Disperz); Commercial — 12 months or duration of request, whichever is less. Continued therapy approvals require documentation of at least 30 days of prior use and clinical response.

Coding and Quantity Limits

HCPCS CodesHCPCS

J7527

Everolimus, oral, 0.25 mg

Afinitor maximum dose

Maximum dose20 mg/day

Typical Afinitor dosing regimen10 mg PO QD (per Dosage & Administration)

Dose contextMaximum applies to multiple oncology indications (breast cancer, PNET, NET, RCC, TSC-AML)

Afinitor tablet limit example

Example Afinitor tablet limitAfinitor: 2 tablets per day (continuation/approval example)

Afinitor Disperz tablet exampleAfinitor Disperz: 4 tablets per day (continuation criteria example)

Maximum daily mg reference

Step Therapy and Prior Therapy Documentation

Requirement	Details / Documentation
Document prior use or failure of indicated prior therapies where required (e.g., endocrine therapy for HR+ breast cancer; prior sunitinib or sorafenib for RCC; other indication-specific prior agents).	Provide date(s) of therapy, agent name(s), reason for discontinuation (lack of efficacy, intolerance, or contraindication), and supporting clinical documentation (office notes, lab results, imaging, or pathology reports).
If generic everolimus is available, document that generic was used or provide clinical rationale why generic is contraindicated or not tolerated.	Prescriber must note if generic everolimus was attempted and include documentation of adverse effects or contraindication when claiming exemption.
For initial requests, include prescriber specialty/consultation as specified by indication (oncologist for oncology indications; nephrologist/hepatologist/transplant specialist for Zortress).	Attach consultation notes or letter of medical necessity documenting specialist involvement.
For transplant (Zortress) requests, document prior failure of tacrolimus for kidney transplant recipients or provide documentation of contraindication/intolerance to tacrolimus.	Include dates and reasons for tacrolimus discontinuation, trough levels if available, and relevant transplant specialist notes.

Coverage requirement	Documentation required
Prior failure of tacrolimus is required for kidney transplant recipients unless tacrolimus is contraindicated or causes clinically significant adverse effects.	Provide documentation of tacrolimus trial and reason for failure or intolerance (e.g., therapeutic drug monitoring, adverse events, clinical notes).
If tacrolimus is contraindicated, document the specific contraindication or clinically significant adverse event that precludes tacrolimus use.	Include treating transplant specialist's statement explaining contraindication and supporting clinical evidence.

Policy update	Effect on authorization / criteria
1Q 2021 annual review: clarified oral oncology generic redirection language and revised approval duration for Commercial to 12 months or duration of request, whichever is less.	Authorization durations updated historically; commercial approvals revised to 12 months (or duration requested) per policy history notes.
1Q 2023 annual review: added age requirements for TSC-SEGA and TSC-associated seizures; consolidated legacy WellCare approval durations to 6 months and clarified adjunctive use for TSC-seizures.	Age minimums and indication-specific approval durations were added; Medicaid/HIM legacy durations consolidated to 6 months per history entries.
1Q 2024 and 1Q 2025 annual reviews: clarifications to generic redirection language, NCCN-related single-agent specifications, and indication list updates (NET revisions and added off-label NCCN-supported uses).	Policy history reflects periodic updates that affected indication wording, single-agent recommendations, and supporting guidance; these changes inform current step-therapy and coverage rules.

Quantity Limits and Dosing Constraints

Afinitor — maximum 20 mg/day (quantity limit)

Quantity limit (Afinitor)Maximum 20 mg/day

Standard regimen noted10 mg PO QD listed under Dosage & Administration

Applies toBreast cancer, PNET, NET, RCC, TSC-AML indications per Dosage & Administration

Afinitor Disperz — example tablet limits

Afinitor Disperz example tablet limit4 tablets per day (continuation criteria example)

Afinitor tablet comparatorAfinitor example: 2 tablets per day referenced alongside Disperz limits

Dose adjustment note

Site of Care Considerations

Note

Zortress is used in multi‑agent transplant regimens

Zortress is used in transplant recipients as part of multi‑agent regimens (for kidney: with basiliximab/Simulect, reduced‑dose cyclosporine, and corticosteroids; for liver: with tacrolimus and corticosteroids) and must be prescribed by the appropriate transplant specialist.

Document the concomitant immunosuppression regimen (e.g., Simulect, cyclosporine, corticosteroids for kidney; tacrolimus and corticosteroids for liver).
Prescriber must be a nephrologist, hepatologist, or transplant specialist.

Note

Home administration and trough‑based dose adjustments for transplant uses

Oral everolimus products are administered in the home setting; for transplant indications dose adjustments should be made to achieve target trough concentrations (Zortress: kidney 0.75 mg BID, liver 1 mg BID; trough targets 3–8 ng/mL; SEGA/TSC and seizure dosing adjusted to 5–15 ng/mL where applicable).

Adjust doses to attain specified trough concentrations per dosing guidance.
Document therapeutic drug monitoring results when relevant to dosing adjustments.

Background — Drug and Mechanism

Everolimus is an mTOR kinase inhibitor available in multiple oral formulations marketed as Afinitor, Afinitor Disperz, and Zortress. The agents are used across oncology indications (including HR+ breast cancer, pancreatic and other neuroendocrine tumors, and renal cell carcinoma), manifestations of tuberous sclerosis complex (SEGA, renal angiomyolipoma, and adjunctive therapy for TSC‑associated seizures), and as immunosuppression for kidney and liver transplant prophylaxis (Zortress) per the product prescribing information.

Definitions and Abbreviations

mTOR inhibitor / Everolimus

DefinitionEverolimus is an mTOR kinase inhibitor marketed as Afinitor, Afinitor Disperz, and Zortress

Clinical uses summarizedUsed for oncology indications (breast cancer, PNET, NET, RCC), tuberous sclerosis complex manifestations (SEGA, renal AML), adjunctive therapy for TSC-associated seizures, and transplant rejection prophylaxis (Zortress)

FormulationsAvailable as Afinitor (tablets), Afinitor Disperz (oral suspension/tablets), and Zortress (tablets)

Abbreviations (selected)

AMLangiomyolipoma

DTCdifferentiated thyroid cancer

Revision History

2025-02-25annual_reviewLatest

1Q 2025 annual review: NET bronchopulmonary language removed per NCCN; SEGA criterion revised; added Qinlock for GIST progression and new off-label NCCN-supported indications (osteosarcoma with Nexavar, meningiomas with bevacizumab or octreotide LAR); references updated.

2024-02-24annual_review

1Q 2024 annual review: clarified generic everolimus redirection; removed DTC requirement for therapy per NCCN; specified single-agent prescribing per NCCN for multiple off-label tumor types; references updated.

2023-02-23

OpenPayer

Everolimus (Afinitor, Afinitor Disperz, Zortress) — Coverage Criteria

Coverage Criteria — Indication-specific Rules

Initial Therapy — Per-Indication Requirements

Continuation / Renewal Criteria and Durations

Provider Requirements and Authorization Workflow

Coding and Quantity Limits

Step Therapy and Prior Therapy Documentation

Quantity Limits and Dosing Constraints

Site of Care Considerations

Background — Drug and Mechanism

Definitions and Abbreviations

Revision History