ModifiedCentenePolicy CP.PHAR.454

Clinical Policy: Avapritinib (Ayvakit)

Defines medical necessity and prior authorization criteria for avapritinib (Ayvakit) for commercial, HIM, and Medicaid lines of business, including initial and continued therapy criteria for GIST and systemic mastocytosis indications.

Policy Summary

PayerCentene

PolicyAvapritinib (Ayvakit) coverage criteria

Policy CodePolicy CP.PHAR.454

Change TypeCriteria revisions and clarifications (material)

Effective DateMar 1, 2020

Next Review Date

Key ActionPrior authorization required; providers must document diagnosis, prescriber specialty, age ≥18, required platelet counts for systemic mastocytosis, relevant mutation status, prior therapy when specified, and that dosing does not exceed plan-approved quantity limits.

SourceLink

POLICY UPDATE CHANGES

For GIST, added Qinlock, Sutent, and Stivarga as examples of prior lines of therapy.

For MLNE and FIP1L1-PDGFRA, revised criteria from 'failure of imatinib' to 'documentation of PDGFRA D842 mutation that is resistant to imatinib'.

Extended initial approval duration from 6 to 12 months for Medicaid/HIM line of business for this maintenance medication.

Added documentation requirement of platelet count 6gt;= 50 x 10^9/L (6gt;= 50,000/mcL) for systemic mastocytosis.

Added oncology bypass language to existing redirections.

Appendix D/E updates: added state IN and revised language and exception for Tennessee regarding step therapy/redirection prohibitions.

3FDA-approved indications listed

12 moTypical approval duration (Medicaid/HIM)

6gt;=50k

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria

General medical necessity

Coverage tied to indication-specific criteria consistent with NCCN and prescribing information; prior therapy and molecular documentation requirements apply where specified.

General coverage requirements: Provider must document indication, required labs (e.g., platelet count for systemic mastocytosis), and relevant molecular testing where applicable (e.g., PDGFRA D842 mutation resistant to imatinib). Requests must not exceed plan-approved quantity limits.

See indication-specific nodes for dosing and prior therapy examples.

Non‑FDA approved indications that are not specifically addressed in this policy will not be authorized unless the provider submits sufficient documentation of efficacy and safety in accordance with applicable off‑label use policies: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, or CP.PMN.53 for Medicaid (or other applicable evidence of coverage documents).

State‑level protections may prohibit step therapy or redirection for advanced/metastatic cancer in certain jurisdictions. See Appendix D for the list of states with prohibitions (for example: FL, GA, IA, IN, LA, MS, NV, OH, OK, PA, TN, TX). Where state law or regulation prohibits redirection for oncology, those protections supersede plan redirection and step therapy rules; the policy also incorporates oncology bypass language to allow appropriate clinical exceptions per plan and state requirements.

Requests that are inconsistent with the indication‑specific criteria in this policy, lack required molecular testing when specified (for example, documentation of a PDGFRA D842 mutation that is resistant to imatinib for MLNE/FIP1L1‑PDGFRA), or exceed health plan‑approved quantity limits may be considered not medically necessary and denied. Providers must submit supporting documentation (office notes, laboratory results, molecular testing reports, or other clinical information) demonstrating that all approval criteria are met.

Initial Therapy Criteria by Indication

Initial therapy

Initial therapy criteria vary by indication and must meet all listed conditions for the relevant diagnosis.

See coverage.criteria_sets for indication-specific initial criteria: Initial therapy criteria are detailed per indication (GIST, AdvSM, ISM, MLNE)

Initial therapy criteria — Updated

Initial therapy requirements updated per 1Q2026 review.

Updated initial therapy notes: For GIST, added examples of acceptable prior lines of therapy including Qinlock (ripretinib), Sutent (sunitinib), and Stivarga (regorafenib). For MLNE/FIP1L1-PDGFRA, documentation must show PDGFRA D842 mutation that is resistant to imatinib (revises prior 'failure of imatinib' wording).

Per 1Q2026 updates.

Continued / Maintenance Therapy Criteria

Continued therapy

Continuation therapy requirements

Continued therapy: Member has been on Ayvakit >=30 days, is responding, and dosing does not exceed indication-specific limits or is supported by literature

Continuation/approval duration — Lines of business

Continuation/maintenance approvals adjusted for lines of business.

Medicaid/HIM continuation duration: Initial approval duration extended from 6 to 12 months for maintenance medication for a chronic condition in the Medicaid/HIM line of business.

Applied to maintenance dosing where applicable.

Prior Authorization and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must document the diagnosis, prescriber specialty, member age (≥ 18 years), single‑agent use, and any indication‑specific requirements (e.g., platelet counts, mutation status, prior therapies or steps) as described in the clinical criteria. Failure to submit required supporting documentation (office chart notes, lab results, molecular testing, prior therapy records, or other clinical information) may result in denial.

Prior authorization required before initiating therapy.
Submit supporting documentation: office notes, lab results (including platelet count for systemic mastocytosis ≥ 50 x 10^9/L), molecular testing reports (PDGFRA exon 18 D842V or PDGFRA D842 mutation resistant to imatinib where applicable), and records of prior therapies or treatment failure when required.
For GIST, document prescriber specialty (oncologist), age ≥ 18, single‑agent use, PDGFRA mutation status OR failure of prior agents (examples include imatinib, ripretinib (Qinlock), sunitinib (Sutent), regorafenib (Stivarga)) unless contraindicated; note state step therapy prohibitions (see Appendix D) and oncology bypass language.
For systemic mastocytosis (ASM, SM‑AHN, MCL, ISM), document prescriber specialty (oncologist, allergist, or immunologist), age ≥ 18, single‑agent use, and platelet count ≥ 50,000/mcL; dose limits and generic‑first language apply.
For MLNE with FIP1L1‑PDGFRA, document hematology/oncology prescriber, age ≥ 18, and PDGFRA D842 mutation resistant to imatinib (not simply imatinib failure).

Step Therapy and Redirection Rules

Requirement	Details
Step therapy requirement
For GIST requests, failure of one of the following prior therapies is required before approval of avapritinib: imatinib, ripretinib (Qinlock), sunitinib (Sutent), or regorafenib (Stivarga), unless contraindicated or clinically significant adverse effects are experienced. Illinois HIM requests are exempt from step therapy as of 1/1/2026 per IL HB 5395.

Requirement	Details
State redirection prohibitions
Follow state-specific prohibitions on redirection/step therapy for advanced or metastatic cancer (see Appendix D). Where a state prohibits step therapy/redirection, those protections apply and redirection may not be enforced; plans should apply oncology bypass language added to redirection rules where applicable.

Laboratory and Dosing Thresholds

inv-10: Platelet count — >= 50 x 10^9/L (>= 50,000/mcL)

Threshold>= 50 x 10^9/L (>= 50,000/mcL)

Applies toAdvanced systemic mastocytosis (ASM, SM-AHN, MCL)

Documentation requirementProvider must include platelet count lab results with prior authorization submission

inv-11: Platelet count — ≥ 50 x 10^9/L (≥ 50,000/mcL)

Threshold≥ 50 x 10^9/L (≥ 50,000/mcL)

ContextRequired laboratory documentation for systemic mastocytosis per NCCN and prescribing information

Submission note

Quantity Limits and Dosing

inv-31: Avapritinib (Ayvakit) — Health plan-approved quantity limit (unspecified in this document)

DrugAvapritinib (Ayvakit)

Quantity limitHealth plan-approved quantity limit applies (specific limit not specified in this document)

RequirementRequest must not exceed plan-approved quantity limit; include quantity details in prior authorization

inv-32: Avapritinib — Plan-approved quantity limit applies

Plan rulePlan-approved quantity limit applies

FrequencyApplied per month or per plan definition as applicable

Implication

Site of Care and Redirection Exceptions

Note

Infusion center — state/plan redirection exceptions and oncology bypass

State and plan-level redirection or step therapy exceptions for oncology may apply at the infusion center or site-of-care; the policy includes oncology bypass language to accommodate these redirection exceptions.

Follow Appendix D state prohibitions and plan-level redirection rules when directing site-of-care decisions.

Definitions

inv-22: AdvSM — Advanced systemic mastocytosis, including aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological ...

TermAdvanced systemic mastocytosis (AdvSM)

IncludesAggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL)

Use in policyReferenced in initial therapy criteria for Avapritinib

inv-23: GIST — Gastrointestinal stromal tumor.

TermGastrointestinal stromal tumor (GIST)

Coverage noteCovered for unresectable, recurrent, progressive, or metastatic GIST with PDGFRA exon 18 mutations per initial therapy criteria

Background

Avapritinib (Ayvakit) is a selective tyrosine kinase inhibitor with FDA‑approved indications that include treatment of unresectable or metastatic gastrointestinal stromal tumor (GIST) with PDGFRA exon 18 mutations, including D842V, and treatment of systemic mastocytosis (advanced and indolent forms) per the product prescribing information. Dosing and monitoring requirements differ by indication; the policy requires documentation of diagnosis, appropriate prescriber specialty, and adherence to indication‑specific dose and laboratory thresholds.