CurrentmhnPolicy CP.PHAR.514

Pralsetinib (Gavreto) Coverage

Defines medical necessity, prior authorization, dosing limits, and continuation criteria for pralsetinib (Gavreto) for commercially insured, HIM/ICHRA, and Medicaid members covered by Centene-affiliated health plans.

Policy Summary

Payermhn

PolicyPralsetinib (Gavreto) Coverage

Policy CodePolicy CP.PHAR.514

Change TypeNo material changes

Effective DateDec 1, 2020

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, RET fusion/pathogenic variant testing, prescriber specialty, age, prior therapy history, and dosing justification if above standard limits.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

400 mg/dayStandard daily dose

800 mg/dayMax dose w/ CYP3A inducer

12 monthsTypical approval duration

≥12 / ≥18Minimum age

100 mg capProduct availability

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Initial Therapy — NSCLC

Initial Approval Criteria — Non-Small Cell Lung Cancer (must meet all):

NSCLC initial criteria: 1. Diagnosis of recurrent, advanced, or metastatic NSCLC; 2. Prescribed by or in consultation with an oncologist; 3. Age >= 18 years; 4. Documentation of RET fusion-positive disease (e.g., CCDC6-RET, KIF5B-RET); 5. Gavreto is not prescribed concurrently with Retevmo; 6. Member has not received prior RET targeted therapy (e.g., Retevmo); 7. Prescribed as a single agent; 8. For Gavreto requests, member must use pralsetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 9. Request meets one of the following (a, b, or c): a) Dose does not exceed both: i) 400 mg per day; ii) 4 capsules per day; b) Both: i) Dose does not exceed both: 1) 800 mg per day; 2) 8 capsules per day; ii) Prescriber attestation of inability to avoid concomitant use of a strong CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort); c) Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Prescribed regimen must be FDA-approved or recommended by NCCN

Initial Therapy — Thyroid Cancer

Initial Approval Criteria — Thyroid Cancer (must meet all):

Thyroid initial criteria: 1. Diagnosis of one of the following: anaplastic thyroid carcinoma (ATC); follicular carcinoma; oncocytic/Hurthle cell carcinoma; papillary carcinoma; or medullary thyroid carcinoma (MTC) [off-label]; 2. Prescribed by or in consultation with an oncologist; 3. Age >= 12 years; 4. Disease is unresectable, recurrent, advanced, or metastatic; 5. Prescribed as a single agent; 6. For ATC, follicular, oncocytic, and papillary carcinoma: documentation of RET fusion-positive disease (e.g., CCDC6-RET, KIF5B-RET) AND one of: i) disease is radioactive iodine-refractory (if radioactive iodine is appropriate) OR ii) for oncocytic carcinoma and ATC, disease is locoregional or metastatic; 7. For MTC: documentation of RET pathologic variant-positive disease (e.g., RET M918T); 8. Gavreto is not prescribed concurrently with Retevmo; 9. Member has not received prior RET targeted therapy (e.g., Retevmo); 10. For Gavreto requests, member must use pralsetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 11. Request meets one of the following (a, b, or c): a) Dose does not exceed both: i) 400 mg per day; ii) 4 capsules per day; b) Both: i) Dose does not exceed both: 1) 800 mg per day; 2) 8 capsules per day; ii) Prescriber attestation of inability to avoid concomitant use of a strong CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort); c) Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Prescribed regimen must be FDA-approved or recommended by NCCN

Initial Therapy — NCCN Compendium Off-label (biliary tract)

Initial Approval Criteria — NCCN Compendium Indications (off-label biliary tract cancers) (must meet all):

NCCN compendium criteria: 1. Diagnosis of one of the following biliary tract cancers: extrahepatic cholangiocarcinoma; intrahepatic cholangiocarcinoma; or gallbladder cancer; 2. Prescribed by or in consultation with an oncologist; 3. Age >= 12 years; 4. Prescribed as a single agent; 5. Documentation of RET fusion-positive disease (e.g., CCDC6-RET, KIF5B-RET); 6. Gavreto is not prescribed concurrently with Retevmo; 7. Member has not received prior RET targeted therapy (e.g., Retevmo); 8. For Gavreto requests, member must use pralsetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 9. Request meets one of the following (a, b, or c): a) Dose does not exceed both: i) 400 mg per day; ii) 4 capsules per day; b) Both: i) Dose does not exceed both: 1) 800 mg per day; 2) 8 capsules per day; ii) Prescriber attestation of inability to avoid concomitant use of a strong CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort); c) Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Prescribed regimen must be FDA-approved or recommended by NCCN

Continuation Therapy

Continued Therapy (All indications in Section I — must meet all):

Continued therapy criteria: 1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Gavreto for a covered indication and has received this medication for at least 30 days; 2. Member is responding positively to therapy; 3. Gavreto is not prescribed concurrently with Retevmo; 4. Member has not received prior RET targeted therapy (e.g., Retevmo); 5. For Gavreto requests, member must use pralsetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 6. If request is for a dose increase, request meets one of the following (a, b, or c): a) New dose does not exceed both: i) 400 mg per day; ii) 4 capsules per day; b) Both: i) New dose does not exceed both: 1) 800 mg per day; 2) 8 capsules per day; ii) Prescriber attestation of inability to avoid concomitant use of a strong CYP3A inducer (e.g., carbamazepine, rifampin, ritonavir, St. John's wort); c) New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Prescribed regimen must be FDA-approved or recommended by NCCN

Dosing and Policy Update Notes

Policy content in this segment indicates dosing and availability and documents historical updates to coverage criteria per NCCN and FDA changes.

Dosing: Recommended dose for NSCLC and thyroid cancer is 400 mg orally once daily; maximum dose of 800 mg/day with coadministration of strong CYP3A inducers; product available as 100 mg capsules.

Prescribed regimen must be FDA-approved or recommended by NCCN; historical policy updates noted

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety in accordance with the plan off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace/ICHRA), or CP.PMN.53 (Medicaid), or unless coverage is supported by the member’s evidence of coverage documents.

Policy history documents that the previously FDA‑approved indication for RET‑mutant medullary thyroid cancer was removed per the product information (prescribing information). This change is recorded in the policy update notes and reflected in the clinical criteria for thyroid cancer.

Initial Authorization Requirements

Initial therapy — Initial authorization nodes include diagnosis-specific testing and prescriber requirements plus dosing limits

Initial authorization nodes include diagnosis-specific testing and prescriber requirements plus dosing limits

Initial authorization nodes: See indication-specific initial criteria: require documentation of RET fusion/variant testing as specified by diagnosis, prescribed by or in consultation with an oncologist, age requirements (>=18 for NSCLC; >=12 for thyroid and biliary tract indications), single-agent use, no concurrent Retevmo, no prior RET-targeted therapy, product preference for pralsetinib if available, and dosing that meets the specified options or has required justification.

Detailed dosing options are in the indication-specific criteria

Initial therapy notes — Policy history indicates addition of single-agent criteria and off-label criteria per NCCN

Policy history indicates addition of single-agent criteria and off-label criteria per NCCN; specific initial therapy criteria are located in the indication sections above.

Initial therapy notes: Historical changes include addition of single-agent therapy criterion for NSCLC and thyroid cancer per NCCN, addition of off-label biliary tract criteria per NCCN, and clarification of thyroid carcinoma subtypes and indications over successive reviews.

See policy history entries for dates of changes

Provider Requirements, Documentation, and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria, including diagnosis, documentation of RET fusion or RET pathogenic variant where indicated, prescriber specialty (oncologist or in consultation with an oncologist), and dosing justification. Requests for pralsetinib (Gavreto) will be reviewed to confirm the regimen is FDA‑approved or recommended by NCCN and that concurrent or prior RET‑targeted therapy (e.g., Retevmo) is not present.

Submit supporting documentation: office notes, pathology/genetic testing showing RET fusion/variant, prior therapy history, and dosing rationale.
Ensure prescriber attestation if higher-than-standard dosing is requested due to unavoidable concomitant strong CYP3A inducer use.
Approval durations and specific operational requirements may vary by line of business (see policy history and plan-specific benefit rules).

Denial Risk

Non‑covered Indications Risk

Requests for indications that are not FDA‑approved and not addressed within this policy are at risk for non‑coverage unless sufficient documentation of efficacy and safety is provided per the applicable off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace/ICHRA, CP.PMN.53 for Medicaid) or other evidence of coverage documents.

Non‑FDA indicated uses require submission of supporting peer‑reviewed literature or guideline recommendations (e.g., NCCN) and will be evaluated under the plan's off‑label criteria.
Examples of off‑label criteria added to this policy historically include certain biliary tract cancers and medullary thyroid carcinoma per NCCN compendium.

Note

Coverage Decisions Subject to Plan Terms

Coverage decisions are subject to all terms, conditions, exclusions, and limitations in the member's coverage documents and to state and federal requirements and applicable Health Plan administrative policies. This clinical policy is a guide to medical necessity and does not guarantee payment.

Refer to the member's evidence of coverage, certificate of coverage, policy, or contract for final benefit determination.
Plan‑level administrative policies and state/federal law take precedence where applicable.

Note

Policy Developed from Prescribing Information and Guidelines

This clinical policy was developed from the Gavreto prescribing information, NCCN guidance, peer‑reviewed literature, and other clinical resources by licensed healthcare professionals. Providers are expected to follow Health Plan administrative policies and submit required documentation for review.

Policy sources include FDA prescribing information, NCCN recommendations, and relevant peer‑reviewed literature.
Providers retain responsibility for clinical judgment and must document rationale when requesting dosing or indications outside standard FDA labeling.

Note

Policy History and Revisions

Policy history: the policy has been updated over time to add single‑agent use criteria per NCCN (including NSCLC and thyroid cancer), to add off‑label criteria for specific tumor types (e.g., biliary tract cancers, MTC per NCCN), and to revise approval durations and line‑of‑business operational details.

2Q 2022: added single‑agent criterion for NSCLC and thyroid cancer updates; introduced oral oncology generic redirection language and commercial approval duration revisions.
2Q 2025–2026: added off‑label criteria for MTC and biliary tract cancers per NCCN; added HIM and ICHRA lines of business and extended Medicaid initial approval duration for maintenance therapy.
Refer to the policy history section for full chronological details of amendments and P&T approval dates.

Documentation Required

Provider Requirements and Dose Justification

Provider action reminders: follow all documentation requirements, attest to absence of prior/concurrent RET‑targeted therapy, and, when applicable, use pralsetinib if available unless contraindicated or clinically intolerable. Dose justification must be submitted for doses exceeding standard limits (e.g., due to strong CYP3A inducer use) or for off‑label practice‑guideline supported dosing.

Do not request concurrent use with Retevmo; prior receipt of RET‑targeted therapy will preclude approval.
Prescriber must indicate if pralsetinib is unavailable or contraindicated to permit use of Gavreto per product preference language.
When requesting doses above standard limits, submit prescriber attestation and supporting evidence or guideline citations.

Dose Limits and Definitions

Dose limits — inv-08: Dose limits — 400 mg/day standard; 800 mg/day maximum when coadministered with strong CYP3A inducers

Standard daily dose400 mg per day (does not exceed 400 mg/day and 4 capsules/day)

Maximum with strong CYP3A inducers800 mg per day (allows up to 8 capsules/day with prescriber attestation of inability to avoid CYP3A inducer)

Capsule limit correspondence4 capsules/day corresponds to 400 mg/day based on 100 mg capsule strength

inv-20: RET fusion-positive — RET fusion-positive disease (definition entry)

DefinitionRET fusion-positive disease: presence of oncogenic RET gene fusions (e.g., CCDC6-RET, KIF5B-RET) documented by testing

Relevance to indicationsRequired documentation for NSCLC, thyroid cancer, and NCCN compendium biliary tract indications

ExamplesReported fusion partners in policy: CCDC6-RET, KIF5B-RET

inv-21: Boxed warning — Boxed warnings include serious infections, including opportunistic infections

Boxed warning summaryBoxed warning: serious infections, including opportunistic infections

Contraindications notedNo contraindications reported in appendix C (policy)

Implication for monitoringProviders should monitor for serious and opportunistic infections per prescribing information

inv-22: non-small cell lung cancer — NSCLC (definition entry)

DefinitionNSCLC (non-small cell lung cancer): recurrent, advanced, or metastatic NSCLC as used in initial approval criteria

Age requirementInitial therapy criteria specify age ≥ 18 years for NSCLC

Testing requirementDocumentation of RET fusion-positive disease required for NSCLC approval (e.g., CCDC6-RET, KIF5B-RET)

inv-23: rearranged during transfection — RET (definition entry)

DefinitionRET: rearranged during transfection — the RET proto-oncogene targeted by pralsetinib

Drug target descriptionPralsetinib inhibits wild-type RET and oncogenic RET fusions and mutations (e.g., RET V804L, V804M, M918T)

Acronym originRET stands for rearranged during transfection as noted in references

OpenPayer

Pralsetinib (Gavreto) Coverage

Coverage and Medical Necessity Criteria

Initial Authorization Requirements

Continued Therapy and Duration

Provider Requirements, Documentation, and Prior Authorization

Dose Limits and Definitions

Step Therapy / Product Preference

Quantity Limits and Capsule Strength

Drug Background and Mechanism

Site of Care Considerations