CurrentmhnPolicy CP.PHAR.90

Crizotinib (Xalkori)

Defines medical necessity, prior authorization, dosing limits, and coverage criteria for crizotinib (Xalkori) for commercial, HIM/ICHRA, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyCrizotinib (Xalkori) coverage criteria

Policy CodePolicy CP.PHAR.90

Change TypeNo material clinical or coverage changes

Effective Date11.01.11

Next Review Date

Key ActionSubmit prior authorization with supporting documentation that the member meets the applicable initial or continuation approval criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 monthstypical approval duration

250 mg BIDNSCLC dosing

500 mg/dayNSCLC max daily

Adults ≥18; Pediatrics ≥1age thresholds

200/250 mgcapsule strengths

Coverage Criteria

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Initial Therapy — NSCLC

Covered when ALL of the following are met for NSCLC initial approval.

ALL of the following

Diagnosis of recurrent, advanced, or metastatic non-small cell lung cancer (NSCLC).
Prescribed by or in consultation with an oncologist.
Age ≥ 18 years.
Tumor demonstrates one of the following biomarkers: ALK-positive, ROS1-positive, MET exon 14 skipping mutation, or high-level MET amplification.
Prescribed as one of the following: - a. As a single agent; OR - b. For high-level MET amplification positive NSCLC with an existing EGFR mutation: crizotinib (Xalkori) may be administered with continuation of osimertinib (Tagrisso).
For Xalkori requests, member must use generic crizotinib if available, unless contraindicated or clinically significant adverse effects are experienced.
Request meets one of the following dosing conditions: - a. Dose does not exceed both of the following: (i) 500 mg per day; AND (ii) either 2 capsules per day or 6 pellets per day; OR - b. 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 — ALCL

Covered when ALL of the following are met for ALCL initial approval.

ALL of the following

Diagnosis of anaplastic large cell lymphoma (ALCL), a peripheral T-cell lymphoma.
Prescribed by or in consultation with an oncologist or hematologist.
Age ≥ 1 year.
Disease is ALK-positive.
Prescribed as a single agent.
Prescribed as treatment for one of the following: (a) palliative intent; OR (b) relapsed or refractory disease.

Initial Therapy — IMT

Covered when ALL of the following are met for IMT initial approval.

ALL of the following

Diagnosis of inflammatory myofibroblastic tumor (IMT).
Prescribed by or in consultation with an oncologist.
Age ≥ 1 year.
Disease is ALK-positive.
Prescribed as a single agent.
For Xalkori requests, member must use generic crizotinib if available, unless contraindicated or clinically significant adverse effects are experienced.

Initial Therapy — Off-label NCCN Compendium Recommended

Covered when ALL of the following are met for Off-label NCCN Compendium recommended indications.

ALL of the following

Prescribed for one of the following diagnoses: (a) histiocytic neoplasm (including Erdheim-Chester disease, Langerhans cell histiocytosis, Rosai-Dorfman disease); (b) cutaneous melanoma; OR (c) uterine inflammatory myofibroblastic tumor (IMT) that is advanced, recurrent, metastatic, or inoperable.
Prescribed by or in consultation with an oncologist or hematologist.
Age ≥ 18 years.
For histiocytic neoplasm or uterine IMT, disease is ALK-positive.
For cutaneous melanoma, all of the following must be met: (a) disease is metastatic or unresectable; (b) disease is ROS1-positive; AND (c) crizotinib (Xalkori) is prescribed as second-line or subsequent therapy.

Initial Therapy Criteria (by indication)

Initial therapy coverage criteria by indication

Initial therapy coverage criteria summarized by indication:

Initial therapy summary: See detailed per‑indication initial therapy criteria: NSCLC (adult, molecular subsets and dosing limits), ALCL (pediatric allowed, ALK‑positive, dosing limits), IMT (pediatric and adult dosing), and NCCN off‑label indications (histiocytic neoplasms, cutaneous melanoma, uterine IMT) including required prescriber specialty, biomarker positivity, single‑agent use, generic preference, and dosing limits or guideline‑supported dosing.

Dosing by indication

Indication‑specific dosing (Indication 1 = dosing regimen; Indication 2 = maximum dose):

NSCLC dosing: Indication 1 (Dosing regimen): 250 mg PO twice daily; Indication 2 (Maximum dose): 500 mg/day

ALCL dosing: Indication 1 (Dosing regimen): 280 mg/m2 PO twice daily; Indication 2 (Maximum dose): 1,000 mg/day

IMT dosing: Indication 1 (Dosing regimen): Pediatric: 280 mg/m2 PO twice daily; Adult: 250 mg PO twice daily. Indication 2 (Maximum dose): Pediatric: 1,000 mg/day; Adult: 500 mg/day

Continuation Therapy Criteria

Continuation criteria

Criteria for continued therapy approval:

Continuation criteria summary: 1. Member currently receiving medication via the Centene benefit, or documentation confirms current receipt for a covered indication with ≥30 days of therapy; 2. Member demonstrates a positive clinical response to therapy; 3. Member must use generic crizotinib if available unless contraindicated; 4. Any requested dose increase must meet the listed dosing limits for the applicable indication (NSCLC/adult IMT limits or ALCL/pediatric IMT limits) or be supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence).

Step	Requirement
1
Generic crizotinib must be used when available unless contraindicated or clinically significant adverse effects are experienced; dosing must not exceed indication-specific maximums (e.g., NSCLC/adult IMT: ≤500 mg/day and either 2 capsules/day or 6 pellets/day) or must be supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

Date/Revision	Policy history note
2Q 2025
Added option for combination use with continued Tagrisso for members with high-level MET amplification and an EGFR mutation per NCCN Compendium.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must demonstrate the member meets the initial approval criteria for the intended indication and submit supporting documentation (office chart notes, lab results, or other clinical information).

Prior authorization required for Xalkori (crizotinib) requests.
Provider must document that all applicable initial approval criteria are met.
Supporting documentation examples: office chart notes, pathology reports, molecular testing results, lab data, and relevant imaging.

Denial Risk

Failure to Meet Criteria May Result in Denial

Requests that do not meet the policy approval criteria, or that are for non‑FDA approved indications not addressed in this policy without sufficient off‑label justification per applicable off‑label policies, may be denied.

Non‑FDA approved indications not addressed in this policy require sufficient documentation of efficacy and safety per off‑label use policies: CP.CPA.09 (commercial), HIM.PA.154 (Health Insurance Marketplace/ICHRA), CP.PMN.53 (Medicaid).
Insufficient or missing clinical documentation may result in denial.

Note

Provider Action — Additional Details May Be in Other Sections

Not all prior authorization triggers or denial operational details are present in this portion of the document; providers should consult the full policy and applicable off‑label policies referenced here for complete prior authorization instructions and denial criteria.

Earlier or other sections of the policy contain specific PA trigger fields, submission instructions, and billing/coding notes.
When in doubt, submit comprehensive clinical documentation and contact the plan/provider portal for PA submission guidance.

Documentation Required

References Cited

References supporting coverage criteria and indications include the Xalkori (crizotinib) Prescribing Information and NCCN guidelines/Compendium. Providers may be asked to supply guideline or literature citations when requesting non‑FDA indicated uses that rely on compendium or peer‑reviewed support.

Primary references: Xalkori Prescribing Information (Pfizer, Sept 2023) and NCCN Compendium/Guidelines (accessed 2026).
For off‑label requests supported by guidelines or literature, prescribers must submit the supporting evidence.

Note

Provider Action — Policy and Coverage Update History

This document records historical updates to step/coverage and clinical criteria (for example: addition of combination use with Tagrisso for high‑level MET amplification and EGFR mutation per NCCN Compendium; changes to initial approval durations; addition of pellet formulation and indication‑specific quantity limits). Providers should note that exceptions or existing prior approvals may apply based on prior authorizations.

Policy history includes additions for combination therapy with Tagrisso (2Q2025), new oral pellet dose form and pellet quantity limits (09.12.23), and revisions to initial/continuation approval durations (2Q2022, 2Q2026).
Existing authorizations and grandfathered exceptions may remain in effect per plan operations.

Quantity Limits

inv-26: Crizotinib — capsule/pellet counts and mg/day limits as specified.

NSCLC (adult) limitMaximum does not exceed 500 mg per day AND either 2 capsules/day or 6 pellets/day.

ALCL (pediatric/other) limitDose does not exceed 560 mg/m2 per day, up to a maximum of 1,000 mg per day AND either 4 capsules/day or 8 pellets/day.

IMT pediatric vs adultPediatric IMT: max 560 mg/m2/day up to 1,000 mg/day (4 capsules or 8 pellets/day). Adult IMT: max 500 mg/day (2 capsules or 6 pellets/day).

inv-27: oral pellets — indication-specific quantity limits (details not included in these chunks).

Pellet quantity limits existIndication-specific quantity limits for oral pellets were added to the policy when oral pellet dose form was introduced.

Policy historyRT4 added new oral pellet dose form per updated prescribing information and added indication-specific quantity limits for pellets (09.12.23).

Details locationSpecific pellet quantity limits are described in the quantity limits section of the policy (see policy tables/quantity limits).

Definitions

inv-19: High-level MET amplification — definition entry.

TermHigh-level MET amplification.

NGS thresholdFor NGS-based testing, defined as gene copy number > 10.

Clinical relevanceEmerging biomarker per NCCN to identify novel therapies for metastatic NSCLC; associated with poor prognosis.

inv-20: Dosing Regimen vs Maximum Dose — distinguishes indication-level dosing regimen and maximum dose.

Dosing Regimen (Indication 1)Specifies the typical per-dose schedule for each indication (e.g., NSCLC: 250 mg PO BID; ALCL: 280 mg/m2 PO BID; IMT pediatric: 280 mg/m2 PO BID; IMT adult: 250 mg PO BID).

Maximum Dose (Indication 2)Specifies the maximum permissible total daily dose for each indication (e.g., NSCLC: 500 mg/day; ALCL: 1,000 mg/day; IMT pediatric: 1,000 mg/day; IMT adult: 500 mg/day).

PurposeDistinguishes the typical regimen a prescriber intends to use from the absolute maximum daily dose allowed by the policy; requests exceeding maximum require guideline/literature support.

Background

Crizotinib (Xalkori) is an oral kinase inhibitor in the ALK/MET tyrosine kinase inhibitor class. It is indicated for treatment of ALK‑ or ROS1‑positive metastatic non‑small cell lung cancer (NSCLC) in adults, ALK‑positive systemic anaplastic large cell lymphoma (ALCL) in patients aged ≥1 year, and unresectable/recurrent/refractory ALK‑positive inflammatory myofibroblastic tumor (IMT) in patients aged ≥1 year. Biomarkers that may guide use in NSCLC include ALK rearrangements, ROS1 rearrangements, MET exon 14 skipping alterations, and high‑level MET amplification; dosing and maximum daily limits vary by indication (for example, NSCLC typical dosing is 250 mg PO BID with a maximum of 500 mg/day, while pediatric ALCL/IMT dosing is weight‑based with a higher per‑day maximum).

OpenPayer

Crizotinib (Xalkori)

Coverage Criteria

Initial Therapy Criteria (by indication)

Continuation Therapy Criteria

Step Therapy

Provider Actions and Requirements

Coding and Definitions

Quantity Limits

Definitions

Background