ModifiedCentenePolicy CP.PHAR.406

Lorlatinib (Lorbrena) coverage for ALK-/ROS1-positive cancers

Defines medical necessity, prior authorization, and coverage criteria for lorlatinib (Lorbrena) for metastatic NSCLC and select NCCN-recommended off-label indications for Centene-affiliated health plans (Commercial, HIM/ICHRA, Medicaid). Affects prescribers, pharmacies, and prior authorization reviewers.

Policy Summary

PayerCentene

PolicyLorlatinib (Lorbrena) coverage for ALK-/ROS1-positive cancers

Policy CodePolicy CP.PHAR.406

Change TypeMaterial updates to prior-therapy options, dosing, and indications

Effective DateMar 1, 2019

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, ALK/ROS1 positivity, prior therapies (if ROS1-positive), prescriber specialty, and dosing within allowed limits.

SourceLink

POLICY UPDATE CHANGES

Added Ibtrozi as an option for required prior failure in ROS1-positive NSCLC and clarified that failure of one of the listed agents is required.

Added maximum dose option of 125 mg per day when receiving a moderate CYP3A4 inducer and removed tablet quantity limit to accommodate dose adjustments.

Added pediatric diffuse high-grade glioma to NCCN-supported off-label indications.

Added Augtyro as a failure option for ROS1-positive disease in prior-therapy list.

Clarified anaplastic large cell lymphoma use is for palliative care or subsequent therapy for relapsed/refractory/progressive disease.

Commercial approval duration revised to '12 months or duration of request, whichever is less'.

100 mg/daystandard ALK-positive dose

125 mg/day

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.

max dose with CYP3A4 inducer

12 monthstypical approval duration

25 mg, 100 mgproduct availability

expandedoff-label indications added

Coverage Criteria

Initial Approval - Non-Small Cell Lung Cancer

Covered when ALL of the following are met:

Initial NSCLC approval: 1. Diagnosis of recurrent, advanced, or metastatic non-small cell lung cancer (NSCLC); 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Tumor is ALK-positive or ROS1-positive (as detected by an FDA-approved test); 5. If ROS1-positive, prior failure of Augtyro, Ibtrozi, Rozlytrek, or Xalkori unless clinically significant adverse effects occurred or all are contraindicated; 6. Prescribed as a single agent; 7. Member uses generic lorlatinib if available unless contraindicated or intolerant; 8. Requested dose meets one of the following: a) does not exceed 100 mg per day; b) does not exceed 125 mg per day if receiving a moderate CYP3A4 inducer; or c) dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Initial Approval - NCCN Recommended Off-Label Uses

Covered when ALL of the following are met for listed NCCN-recommended diagnoses:

NCCN off-label uses: 1. Prescribed for one of the following NCCN-recommended diagnoses: a) anaplastic large cell lymphoma (ALCL); b) diffuse large B-cell lymphoma (relapsed or refractory); c) Erdheim‑Chester disease (symptomatic or relapsed/refractory); d) inflammatory myofibroblastic tumor (IMT); e) uterine IMT that is advanced, recurrent, metastatic, or inoperable; f) pediatric diffuse high-grade glioma; 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age meets the diagnosis-specific requirement: for pediatric diffuse high-grade glioma < 18 years; for all other NCCN-recommended uses ≥ 18 years; 4. Disease is ALK-positive; 5. Prescribed as a single agent; 6. For ALCL: intended use is palliative OR subsequent therapy for relapsed, refractory, or progressive disease; 7. For pediatric diffuse high-grade glioma: prescribed as adjuvant treatment (with specified exceptions) OR for treatment of recurrent/progressive disease (with specified exceptions); 8. Member uses generic lorlatinib if available unless contraindicated or intolerant; 9. Requested dose meets one of the following: a) does not exceed 100 mg per day; b) does not exceed 125 mg per day if receiving a moderate CYP3A4 inducer; or c) dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).

Continuation Therapy

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

Continuation: 1. Member is currently receiving lorlatinib via the Centene benefit or documentation shows the member has received lorlatinib for at least 30 days for a covered indication; 2. Member is responding positively to therapy; 3. Member uses generic lorlatinib if available unless contraindicated or intolerant; 4. If request is for a dose increase, the new dose meets one of the following: a) does not exceed 100 mg per day; b) does not exceed 125 mg per day if receiving a moderate CYP3A4 inducer; or c) new dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).

Coverage criteria summary

Coverage is provided when policy-specified clinical criteria are met, including prior therapy failure requirements and dosing considerations per NCCN updates.

ROS1-positive NSCLC prior therapy: Member has ROS1-positive NSCLC and has failed one of the listed ROS1-targeted agents (Augtyro, Ibtrozi, Rozlytrek, or Xalkori); failure of one listed agent is required unless contraindicated or clinically significant adverse effects are experienced.failure of one listed agent

Updated 2Q 2026 to add Ibtrozi and clarify 'or' logic; prior-agent list has been revised per NCCN.

Dosing options: Maximum dose is typically 100 mg once daily; an option of 125 mg per day is allowed if the member is receiving a moderate CYP3A4 inducer; tablet quantity limits were removed to accommodate dose adjustments.100 mg or 125 mg with moderate CYP3A4 inducer

Updated 2Q 2026.

Approval duration:

Non‑FDA approved indications that are not specifically addressed in this clinical policy are not authorized for coverage unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policy (Commercial: CP.CPA.09; HIM/ICHRA: HIM.PA.154; Medicaid: CP.PMN.53) or unless the member's evidence of coverage allows the use.

When state Medicaid coverage provisions conflict with this clinical policy, the state Medicaid provisions take precedence. Coverage determinations are also subject to the terms, conditions, exclusions, and limitations of the member's coverage documents (for example, evidence of coverage or certificate of coverage) and to applicable Health Plan‑level administrative policies and state and federal requirements.

Uses that are non‑FDA approved and not addressed in this policy are considered not authorized unless the provider supplies adequate off‑label efficacy and safety documentation per the referenced off‑label use policies or the member's coverage documents. Requests lacking such documentation may be denied.

This clinical policy is intended to guide medical necessity determinations; it is one component used to assist coverage decisions and benefit administration. Specific conditions that are deemed not medically necessary (NMN) are defined elsewhere in the full policy set or in the member's benefit documents and are contingent on the member's coverage terms and applicable regulatory requirements.

Coding and Dose Limits

NDC / Drug CodesNDC

NDC not listed

No NDC codes provided in this document

Codes referencedmixed

N/A	No explicit CPT/HCPCS/ICD-10/NDC codes provided in this document portion

Dose limits

Standard daily dose100 mg per day (lorlatinib)

Allowed increased dose with moderate CYP3A4 inducerUp to 125 mg per day if receiving a moderate CYP3A4 inducer

AdministrationOral, single-agent use as specified in policy criteria

Maximum dose when on moderate CYP3A4 inducer

Maximum dose on moderate CYP3A4 inducer125 mg per day

ContextPermitted only when member is receiving a moderate CYP3A4 inducer per policy dosing rules

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for Lorbrena (lorlatinib). Providers must document diagnosis, tumor biomarker status (ALK or ROS1 positivity), prior therapies when applicable, prescriber specialty (oncologist or hematologist as specified), and treatment intent. Requests for NCCN-recommended off‑label uses must reference supporting guidelines or peer‑reviewed literature when indicated.

Prior authorization may be required for listed ROS1 agents (Augtyro™, Ibtrozi™, Rozlytrek™, Xalkori®) per Therapeutic Alternatives and plan requirements.
Prescriptions must be by or in consultation with an oncologist (or hematologist for hematologic indications).
Dose limits: ≤100 mg/day (standard); ≤125 mg/day if receiving a moderate CYP3A4 inducer; doses above these must be supported by guidelines or literature and prescriber must submit evidence.

Denial Risk

Denial Triggers

Background

Lorlatinib (Lorbrena) is an anaplastic lymphoma kinase (ALK) and ROS1 kinase inhibitor indicated for adult patients with metastatic ALK‑positive non‑small cell lung cancer (NSCLC). This clinical policy covers FDA‑approved ALK‑positive NSCLC and also permits select NCCN‑supported off‑label indications

Definitions

ALK — definition

TermALK

DefinitionAnaplastic lymphoma kinase

Usage noteRequired biomarker for FDA-approved NSCLC indication and some NCCN-supported off-label uses

IMT — definition

TermIMT

DefinitionInflammatory myofibroblastic tumor

ContextIncluded among NCCN-supported off-label indications in policy (e.g., uterine IMT) when criteria are met

Line of Therapy

subsequent

Subsequent therapy intent: Use as subsequent therapy (e.g., for anaplastic large cell lymphoma: palliative OR subsequent therapy for relapsed/refractory/progressive disease).

second-line

Policy-defined second-line use: For ROS1-positive NSCLC, lorlatinib is considered only after failure of a specified ROS1-targeted agent (Augtyro, Ibtrozi, Rozlytrek, or Xalkori) unless contraindicated or intolerant; for ALK-positive NSCLC, lorlatinib may be used per FDA indication without the ROS1-specific prior therapy requirement.

second-line

Second-line—ALCL clarification: Anaplastic large cell lymphoma (ALCL) use: lorlatinib is authorized as subsequent therapy for relapsed, refractory, or progressive disease and may be used for palliation per NCCN guidance.

Biomarker and Diagnostic Requirements

ALK — biomarker requirement

BiomarkerALK positive as detected by an FDA-approved test

Required forFDA-approved indication: metastatic ALK-positive non-small cell lung cancer

VerificationDocumentation of FDA-approved test result required for prior authorization

ROS1 — biomarker requirement

BiomarkerROS1 positive as detected by an FDA-approved test

Required forROS1-positive NSCLC coverage pathway (step therapy and prior-failure requirements apply)

Documentation

Covered Regimens and Dosing

Regimen	Indication	Coverage
Lorlatinib 100 mg orally once daily; allowance up to 125 mg/day if receiving a moderate CYP3A4 inducer	ALK-positive non‑small cell lung cancer (adult)	Covered when policy criteria are met (see coverage criteria); single‑agent use; dose must not exceed 100 mg/day unless patient is receiving a moderate CYP3A4 inducer (125 mg/day maximum)

Regimen	Indication	Prior therapy requirement	Coverage
Single‑agent lorlatinib (Lorbrena); dosing per policy (standard 100 mg PO once daily; up to 125 mg/day if receiving a moderate CYP3A4 inducer)	ROS1‑positive non‑small cell lung cancer	Member must have failed one of the listed ROS1‑targeted agents (Augtyro, Ibtrozi, Rozlytrek, or Xalkori) unless contraindicated or intolerant	Covered when policy criteria are met (including documented ROS1 positivity and required prior therapy failure)

Policy Summary

PayerCentene

PolicyLorlatinib (Lorbrena) coverage for ALK-/ROS1-positive cancers

Policy CodePolicy CP.PHAR.406

Change TypeMaterial updates to prior-therapy options, dosing, and indications

Effective DateMar 1, 2019

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, ALK/ROS1 positivity, prior therapies (if ROS1-positive), prescriber specialty, and dosing within allowed limits.

SourceLink

On This Page

Initial approval durations standardized: Medicaid/HIM/ICHRA initial approvals are 12 months; Commercial approvals are 12 months or duration of request, whichever is less.

Updated 2022–2026 reviews.

Supported indications: Policy includes FDA‑approved ALK-positive NSCLC and NCCN‑supported off‑label indications such as DLBCL, Erdheim‑Chester disease, IMT (including uterine IMT), pediatric diffuse high-grade glioma, and anaplastic large cell lymphoma (as subsequent or palliative therapy per NCCN).N/A

Added across 2022–2026 reviews.

Prescriber must document dosing rationale or adherence to practice guidelines if exceeding standard dose

Requests that do not include sufficient documentation to demonstrate that all approval criteria are met, or requests for non‑FDA indications not addressed by this policy without sufficient off‑label evidence (per CP.CPA.09, HIM.PA.154, CP.PMN.53 as applicable), are subject to denial.

Lack of documentation of prior failure of required ROS1 agents for ROS1‑positive NSCLC (unless intolerance or contraindication documented) is a common denial trigger.
Requests exceeding dose limits without supportive evidence or lacking prescriber specialty documentation may be denied.
Off‑label uses without NCCN support or adequate peer‑reviewed evidence per plan off‑label policy may be denied.

Documentation Required
Required Documentation
Provider must submit documentation (such as office chart notes, laboratory results, pathology or molecular testing reports, and other pertinent clinical information) that supports the member has met all applicable approval criteria. For off‑label NCCN recommended uses, the prescriber must submit supporting evidence when requested.
Include documentation of ALK or ROS1 positivity (molecular/pathology report).
For ROS1‑positive NSCLC, document prior therapy and failure or intolerance of one of the listed ROS1 agents when required.
Submit prior treatment records, dates, and reasons for discontinuation (progression, intolerance, contraindication).

Documentation Required
Documentation and Jurisdictional Precedence
Coverage decisions are subject to the member's evidence of coverage, plan terms, state and federal requirements, and Health Plan‑level administrative policies. For Medicaid members, state Medicaid coverage provisions take precedence when they conflict with this clinical policy.
Follow applicable off‑label and prior authorization administrative policies (e.g., CP.CPA.09, HIM.PA.154, CP.PMN.53) when requesting coverage for non‑FDA indications.
Health Plan may have additional submission or notification requirements; confirm with the member's specific plan and evidence of coverage.

Prior Authorization
Prior Therapy Requirement for ROS1‑Positive NSCLC
For ROS1‑positive NSCLC, prior therapy requirements apply: the member must have experienced failure of one of the listed ROS1‑targeted agents (Augtyro™, Ibtrozi™, Rozlytrek™, or Xalkori®) unless clinically significant adverse effects are documented or all are contraindicated. Prior authorization for those agents may be required per plan.
Failure of one of the listed ROS1 agents is required prior to approval unless there is documented intolerance or contraindication.
Therapeutic alternatives and dosing for the listed agents are in Appendix B (Rozlytrek®, Xalkori®, Augtyro™, Ibtrozi™).

Step Therapy
Step Therapy for ROS1‑Positive NSCLC
Step therapy: for ROS1‑positive NSCLC, approval for Lorbrena requires prior failure of at least one of the specified ROS1‑targeted agents (including Ibtrozi and Augtyro among others) per the policy criteria; exceptions may be made for documented intolerance or contraindication.
Document prior agent used, dates of therapy, and reason for discontinuation (progression, adverse event, or contraindication).
Prior authorization may be required for the ROS1 agents listed in the therapeutic alternatives appendix.

NCCN-supported off-label indication

TermNCCN-supported off-label indication

DefinitionUse of lorlatinib for cancer types not FDA-labeled but supported by NCCN recommendations

ExamplesDiffuse large B-cell lymphoma, Erdheim-Chester disease, IMT (including uterine IMT), pediatric diffuse high-grade glioma, anaplastic large cell lymphoma

subsequent therapy

Added/clarified in 2Q 2026 review.

Provider must document positive ROS1 test result for prior authorization

ROS1 — additional criteria and notes

Updated step-therapy noteFor ROS1-positive NSCLC, prior failure of one of the listed ROS1-targeted agents is required (agents list updated to include Ibtrozi and Augtyro among others)

Agent examplesAugtyro, Ibtrozi, Rozlytrek, Xalkori (failure of one required unless contraindicated or intolerant)

Policy impactPrior authorization reviewers should confirm documented prior failure of one listed ROS1 agent before approving lorlatinib for ROS1-positive disease