CurrentCentenePolicy CP.PHAR.441

Entrectinib (Rozlytrek) (PDF)

Defines medical necessity criteria, dosing limits, age and diagnostic requirements, prior authorization/documentation expectations, approval durations, and excluded indications for entrectinib (Rozlytrek) across Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyEntrectinib (Rozlytrek) (PDF)

Policy CodePolicy CP.PHAR.441

Change TypeAnnual/revisions

Effective DateDec 1, 2019

Next Review Date

Key ActionProvider must submit documentation (office notes, lab results, or other clinical information) supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

4Q 2025 annual review revised NTRK fusion-positive solid tumor section to NTRK fusion-positive cancer to include off-label non-solid tumor indications and added histiocytic neoplasms criteria.

4Q 2024 annual review added requirement for NSCLC use as a single agent and for NTRK solid tumors added requirement for recurrent or unresectable disease and single agent use.

RT4 (11.20.23) updated pediatric age limit to >1 month from ≥ 12 years per FDA pediatric extension; updated recommended dosages per PI; added oral pellet formulation; removed exclusion for prior ROS1 therapy in NSCLC.

Revised approval duration for Commercial line of business to 12 months or duration of request, whichever is less (effective 01.20.22; P&T 05.22).

3Covered indications

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Coverage Summary

Coverage stance: covered with criteria for ROS1-positive metastatic NSCLC, NTRK fusion-positive cancers (including pediatric patients > 1 month), and ROS1-positive melanoma (off-label) per policy. The NTRK indication is an accelerated approval based on tumor response and durability and continued approval may depend on confirmatory trials. The policy aligns with FDA labeling, NCCN recommendations, and Centene formulary rules including a generic-first directive for brand Rozlytrek requests. Effective date: 12.01.19; Last review date: 11.25.

Initial Therapy Criteria

Continuation Therapy Criteria

Unapproved / Not Authorized Indications

Provider Actions

Documentation Required

Submit supporting documentation

Submit office chart notes, laboratory results, or other clinical information that documents the member meets all approval criteria for the requested use. Examples include diagnostic test results (e.g., ROS1 or NTRK testing), prior therapy history, dosing rationale, and clinical assessments supporting necessity.

Prior Authorization

Prescriber specialty and prior therapy

Ensure the prescription is written by or in consultation with the required specialist: an oncologist for most NTRK fusion-positive cancers and NSCLC, or a hematologist when the request is for a histiocytic neoplasm. For NTRK indications, document that the member has not received prior NTRK-targeted therapy (for example, Vitrakvi or Augtyro).

Billing Rule

Generic product required when available

For brand Rozlytrek requests, the member must use generic entrectinib if a generic is available unless the member has a contraindication or clinically significant adverse effects to the generic. This generic-first requirement applies to initial and continued therapy and to requests for dose increases.

Documentation Required

Body surface area documentation for pediatrics/NTRK

Document the member's current body surface area (BSA in m2) when determining pediatric dosing and for all NTRK fusion-positive cancer dosing decisions per policy dosing bands.

Denial Risk

Dose limits enforcement

Requests with doses that exceed the policy-specified maximums for adults or the BSA-based pediatric limits require supporting evidence from practice guidelines or peer-reviewed literature; without such support they may be denied. Adult maximums include 600 mg/day, 3 capsules/day, and 12 packets/day; pediatric maximums are defined by BSA bands and age-based limits (including ≤250 mg/m2/day for age >1 month to ≤6 months).

Documentation Required

Response documentation for continued therapy

For continued therapy, submit documentation that the member has received at least 30 days of prior therapy and is responding positively to treatment (clinical assessments, imaging, or other objective evidence).

Applicable Codes & Product Availability

Product availability (dosage forms)NDC|mixed

Capsules: 100 mg, 200 mg	Rozlytrek capsule strengths available
Pellet: 50 mg	Oral pellet formulation available

Clinical Evidence

Primary evidence source: Rozlytrek Prescribing Information (Genentech), January 2024. Guideline sources: NCCN Drugs & Biologics Compendium and NCCN Non-Small Cell Lung Cancer v7.2025. Background notes: the NTRK approval is an accelerated approval based on tumor response rate and durability of response per the FDA PI.

Background & Definitions

Background: Entrectinib (Rozlytrek) is FDA-approved for ROS1-positive metastatic NSCLC (adults) and for adult and pediatric patients > 1 month with NTRK gene fusion-positive tumors that are metastatic, unresectable, or progress after or lack satisfactory alternative therapy. The NTRK indication is an accelerated approval based on tumor response and durability; continued approval may depend on confirmatory trials. The policy mirrors FDA and NCCN guidance and Centene formulary requirements, including a generic-first directive for brand Rozlytrek. Product availability includes capsules (100 mg, 200 mg) and an oral pellet 50 mg formulation; pediatric dosing was updated per the PI.

Glossary: BSA — body surface area (m2); NTRK — neurotrophic tyrosine receptor kinase gene fusions; NSCLC — non-small cell lung cancer.

Revision History

4Q 2025 (Date = 07.25.25; P&T Approval Date = 11.25)revisedLatest

Revised NTRK fusion-positive solid tumor section to NTRK fusion-positive cancer to include off-label non-solid tumor indications; added histiocytic neoplasms criteria with allowance for hematology specialty; added option for advanced disease for solid tumors; revised maximum capsules for pediatrics per PI; extended initial approval duration for Medicaid and HIM from 6 months to 12 months.

4Q 2024 (Date = 08.07.24; P&T Approval Date = 11.24)revised

For NSCLC, added requirement for use as a single agent; for NTRK solid tumors, added requirement for recurrent or unresectable disease and requirement for single agent use.