Centene everolimus Coverage & Prior Auth Update

Coverage Criteria — Indication-specific and General Rules

Prophylaxis of Organ Rejection

Covered when ALL of the following are met:

Zortress transplant prophylaxis criteria: 1) Request is for Zortress; 2) Member has received or is scheduled for a kidney or liver transplant; 3) Prescribed by or in consultation with a nephrologist, hepatologist, or transplant specialist; 4) Age >= 18 years; 5) For kidney transplant, failure of tacrolimus unless contraindicated or intolerant; 6) Use generic everolimus if available unless contraindicated; 7) Prescribed in combination with specified agents (kidney: Simulect, cyclosporine, corticosteroids; liver: tacrolimus and corticosteroids); 8) Request does not exceed health plan quantity limits.

All conditions must be met

NCCN Compendium Indications (off‑label)

Covered when ALL of the following are met:

NCCN off‑label indications: 1) Request is for Afinitor or Afinitor Disperz; 2) Diagnosis is one of the specified tumor types or combinations per policy (e.g., HL, WM/LPL, thymoma/thymic carcinoma, PEComa, recurrent angiomyolipoma, lymphangioleiomyomatosis, histiocytic neoplasms, endometrial carcinoma with letrozole, GIST with specified combinations after progression, DTC, osteosarcoma with Nexavar, meningiomas with bevacizumab or octreotide LAR); 3) Prescribed by or in consultation with an oncologist; 4) Age >= 18 years; 5) Use generic everolimus if available unless contraindicated; 6) Request does not exceed health plan quantity limits; 7) Dose is within FDA maximum or supported by practice guidelines/peer‑reviewed literature (prescriber must submit supporting evidence).

Prescribed regimen must be FDA‑approved or recommended by NCCN

All Indications — Continuation/Current Therapy

Covered when ALL of the following are met:

Ongoing therapy criteria: 1) Member currently receiving medication via Centene benefit, or documentation supports at least 30 days of current therapy; 2) Member is responding positively to therapy; 3) Use generic everolimus if available unless contraindicated or clinically significant adverse effects are experienced; 4) Request does not exceed health plan quantity limits; 5) For dose increases (except partial‑onset seizures associated with TSC, SEGA associated with TSC, and organ rejection prophylaxis), new dose must not exceed 20 mg/day and product-specific tablet limits OR be supported by practice guidelines/peer‑reviewed literature (prescriber must submit supporting evidence).

See policy for exceptions

Other/Unlisted Indications

If not specifically listed, follow one of the following:

Path for recently changed labels or unlisted uses: 1) If label changed within last 6 months and policy not updated, refer to formulary/no‑coverage or non‑formulary policies per line of business; OR 2) If requested use not listed in section III and criterion 1 does not apply, refer to the off‑label use policy for the relevant line of business (CP.CPA.09 commercial, HIM.PA.154 marketplace, CP.PMN.53 Medicaid).

Provider must follow referenced policies

Afinitor is not indicated for the treatment of patients with functional carcinoid tumors. This limitation is stated in the product labeling and the clinical policy; requests for Afinitor to treat functional carcinoid tumors should not be approved under this policy.

Non‑FDA approved indications that are not specifically addressed in this policy are excluded unless the prescriber supplies sufficient documentation of efficacy and safety consistent with the applicable off‑label use policy: CP.CPA.09 (commercial), HIM.PA.154 (health insurance marketplace), or CP.PMN.53 (Medicaid). When submitting an off‑label request, include supporting evidence (peer‑reviewed literature, guideline recommendations, or NCCN compendium support) as required by those referenced policies.

For Medicaid members, state Medicaid coverage provisions take precedence when they conflict with the coverage provisions in this clinical policy. Providers should consult the applicable state Medicaid manual for any differing coverage rules or requirements.

Use of everolimus for non‑FDA approved indications that are not addressed in this policy without adequate off‑label documentation is considered not authorized. Providers must submit the documentation required by the off‑label use policies referenced in this policy to support coverage for such indications.

Initial Therapy — Indication-specific Authorization Rules

inv-38: Initial therapy per indication

Initial approval is indication-specific; each section requires meeting all listed criteria.

Initial therapy per indication: Initial approval is indication-specific; each section requires meeting all listed criteria.

See coverage criteria sections A–G for full criteria

inv-39: Initial Therapy — Initial therapy coverage for specific indications requires:

Initial therapy coverage for specific indications requires:

Initial therapy for Zortress transplant: Request for Zortress for kidney or liver transplant prophylaxis must be prescribed by appropriate specialist, meet age and combination therapy requirements, and for kidney transplant require prior tacrolimus failure unless contraindicated; use generic when available.

Quantity limits apply

Continuation Therapy — Renewal and Ongoing Use

inv-41: Continuation Therapy — Continuation requests must meet all listed criteria

Continuation requests must meet all listed criteria

Continuation criteria: Member is currently receiving the medication via Centene benefit or has received it for at least 30 days; member is responding positively to therapy; use generic everolimus if available unless contraindicated; request does not exceed health plan quantity limits; dose increases limited as specified.

See exceptions for TSC/SEGA/organ rejection prophylaxis

inv-42: CONTINUATION CRITERIA — Document history indicates continued therapy provisions and PA duration adjustments

Document history indicates continued therapy provisions and prior authorization duration adjustments

CONTINUATION CRITERIA history note: Document history: continued therapy provisions and prior authorization durations updated (COC applied to Zortress in continued therapy).

Refer to policy history for details

Step Therapy and Prior Treatment Requirements

Step requirement	Applies to / Notes
Prior therapy failure or documented history of prior therapy is required unless contraindicated or clinically significant adverse effects are experienced.
Applies across multiple initial‑therapy indications (examples: history of endocrine therapy for HR+ breast cancer; prior systemic therapy for relapsed or metastatic RCC) — see indication‑specific criteria and Appendix B for prior therapies.

Step requirement	Applies to / Notes
Failure of tacrolimus is required prior to use of Zortress for kidney transplant prophylaxis unless tacrolimus is contraindicated or clinically significant adverse effects are experienced.
Specific to kidney transplant prophylaxis with Zortress; combination therapy and specialist prescriber requirements also apply (see prophylaxis criteria).

Step requirement	Applies to / Notes
Prior‑therapy requirement for differentiated thyroid carcinoma (DTC) was removed in accordance with NCCN guidance.
Document history: prior‑therapy clarifications and removals (including DTC) were applied per NCCN updates during policy review; follow current NCCN recommendations for DTC and other clarified indications.

Provider Actions — Prior Authorization, Documentation, and Supporting Evidence

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office chart notes, lab results, operative or pathology reports, and other clinical information) demonstrating the member meets the indication‑specific criteria in this policy. Failure to provide sufficient supporting documentation may result in denial of the request.

Prior authorization required for Afinitor, Afinitor Disperz, and Zortress.
Provider should document diagnosis, prior therapies, treatment response, prescriber specialty, age, and any contraindications or intolerances to alternative therapies.

Prior Authorization

Prior Authorization Durations and Quantity Limits

Initial approvals and continuation approvals have defined durations and quantity limits. Requests must not exceed health plan‑approved quantity limits when applicable.

Initial approval durations for maintenance indications have been extended to 12 months (or duration of request, whichever is less) for applicable commercial lines of business per review updates.
If a request exceeds the health plan‑approved quantity limit, clinical justification and supporting evidence must be provided.

Coding — HCPCS and Dose/Concentration Reference

HCPCSHCPCS

J7527

Everolimus, oral, 0.25mg

Maximum daily dose

Maximum daily dose20 mg per day

Afinitor tablet limitMaximum 2 tablets per day

Afinitor Disperz tablet limitMaximum 4 tablets per day

Maximum daily dose for dose increase

Dose increase maximumNew dose must not exceed 20 mg/day unless supported by guidelines or peer‑reviewed literature (prescriber must submit supporting evidence)

Product tablet limits applyAfinitor: 2 tablets/day; Afinitor Disperz: 4 tablets/day

Exceptions

Quantity Limits and Product-specific Tablet Limits

everolimus (Afinitor/Afinitor Disperz)

Overall maximum daily dose20 mg per day (all products)

Afinitor tablet limitMaximum 2 tablets per day

Afinitor Disperz tablet limitMaximum 4 tablets per day

Product-specific dosing noteDosing and maximums for TSC/SEGA and transplant may be based on trough concentrations rather than fixed mg/day

Everolimus (all products) — Quantity limits

Health plan quantity limitRequests must not exceed the health plan‑approved quantity limit, if applicable

Generic use requirement

Definitions and Abbreviations

Abbreviations

DTCdifferentiated thyroid carcinoma

GIgastrointestinal

HLHodgkin lymphoma

PNETpancreatic neuroendocrine tumor

NETneuroendocrine tumor

RCCrenal cell carcinoma

STS/PEComasoft tissue sarcoma / perivascular epithelioid cell tumor

Background — Drug Description and Indications Summary

Everolimus is an oral mTOR kinase inhibitor marketed under multiple product names: Afinitor and Afinitor Disperz (oncology and TSC indications) and Zortress (immunosuppressant for transplant prophylaxis). Product labeling specifies different indications and age ranges for each product and includes important limitations of use (for example, Afinitor is not indicated for functional carcinoid tumors; Zortress has transplant‑specific limitations). Refer to the prescribing information for exact dosing, age indications, and combination regimens.

OpenPayer

Clinical Policy: Everolimus (Afinitor, Afinitor Disperz, Zortress) coverage

Coverage Criteria — Indication-specific and General Rules

Initial Therapy — Indication-specific Authorization Rules

Continuation Therapy — Renewal and Ongoing Use

Step Therapy and Prior Treatment Requirements

Provider Actions — Prior Authorization, Documentation, and Supporting Evidence

Coding — HCPCS and Dose/Concentration Reference

Quantity Limits and Product-specific Tablet Limits

Definitions and Abbreviations

Background — Drug Description and Indications Summary