Centene tucatinib (Tukysa) Coverage Update

Coverage Criteria

Initial Therapy — Breast Cancer

Covered when ALL of the following are met

Breast Cancer initial criteria: 1. Diagnosis of advanced, unresectable, or metastatic breast cancer; 2. Confirmation of HER2 positive disease; 3. Prescribed by or in consultation with an oncologist; 4. Age >= 18 years; 5. Failure of one or more anti-HER2 based regimens in the metastatic setting (see Appendix B) unless clinically significant adverse effects or contraindications; 6. Prescribed in combination with trastuzumab and capecitabine; 7. For Tukysa requests, member must use tucatinib if available unless contraindicated or clinically significant adverse effects are experienced; 8. Request meets one of the following: (a) Dose does not exceed both: (i) 600 mg per day and (ii) 4 tablets 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).dose <= 600 mg/day and <= 4 tablets/day

Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy — Colon/Rectal/Appendiceal Adenocarcinoma

Covered when ALL of the following are met

Colorectal initial criteria: 1. Diagnosis of advanced, unresectable, or metastatic colon cancer, rectal cancer, or appendiceal adenocarcinoma; 2. Disease is HER2 positive (amplified) and RAS (both KRAS and NRAS) wild-type; 3. Prescribed by or in consultation with an oncologist; 4. Age >= 18 years; 5. No previous use of a HER2 inhibitor therapy; 6. Prescribed in combination with trastuzumab; 7. One of the following: (a) Disease has progressed following a fluoropyrimidine-, oxaliplatin-, or irinotecan-based regimen; OR (b) Both: (i) Disease is BRAF wild-type; and (ii) Prescribed as initial systemic therapy when intensive therapy is not recommended; 8. For members with dMMR/MSI-H or POLE/POLD1 mutation, member is ineligible for, or disease has progressed on, checkpoint inhibitor immunotherapy; 9. For Tukysa requests, member must use tucatinib if available unless contraindicated or clinically significant adverse effects are experienced; 10. Request meets one of the following: (a) Dose does not exceed both: (i) 600 mg per day and (ii) 4 tablets 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).dose <= 600 mg/day and <= 4 tablets/day

Prescribed regimen must be FDA-approved or recommended by NCCN.

Initial Therapy — Biliary Tract Cancers (off-label)

Covered when ALL of the following are met

Biliary tract initial criteria: 1. Diagnosis of biliary tract cancer (gallbladder cancer, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma) that is unresectable, resected gross residual (R2), or metastatic; 2. Disease is HER2 positive; 3. Prescribed by or in consultation with an oncologist; 4. Age >= 18 years; 5. Prescribed in combination with trastuzumab; 6. Prescribed as subsequent (subsequent-line) therapy; 7. For Tukysa requests, member must use tucatinib if available unless contraindicated or clinically significant adverse effects are experienced; 8. Dose is within the FDA maximum limit for any FDA-approved indication or 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 — All Indications

Continued coverage when ALL of the following are met

Continuation criteria: 1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tukysa for a covered indication and has received this medication for at least 30 days; 2. Member is responding positively to therapy; 3. If request is for a dose increase, request meets one of the following: (a) New dose does not exceed both: (i) 600 mg per day and (ii) 4 tablets per day; OR (b) New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).dose <= 600 mg/day and <= 4 tablets/day

Prescribed regimen must be FDA-approved or recommended by NCCN.

Indication-specific prior therapy requirements (summary)

Policy includes indication-specific requirements and prior therapy requirements per annual reviews and RT updates.

Colorectal cancer (dMMR/MSI-H): Per 3Q 2023 annual review and NCCN recommendations, patients with dMMR/MSI-H colorectal cancer must receive checkpoint inhibitor immunotherapy prior to tucatinib unless ineligible or progressed on that therapy.

Added 3Q 2023 annual review

Colorectal cancer alternative: POLE/POLD1 mutation option if member is ineligible for, or disease has progressed on, checkpoint inhibitor immunotherapy.

Added 3Q 2024

HER2-positive disease: Redirection language revised to require failure of one or more anti-HER2 based regimens for HER2-positive disease prior to tucatinib in applicable settings.

3Q 2022 annual review

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 applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid), or other applicable evidence of coverage documents.

Appendix C — Contraindications/Boxed Warnings: None reported.

Uses for non‑FDA approved indications that lack sufficient documentation of efficacy and safety per the referenced off‑label use policies are not authorized.

No specific Not Medically Necessary (NMN) statements are included in this excerpt; prior reviews are noted as reporting no significant changes where applicable.

Initial Therapy

Initial Therapy — Initial authorization criteria by diagnosis

Initial authorization criteria by diagnosis

See Initial Therapy criteria: Refer to diagnosis-specific initial criteria for breast cancer, colorectal cancer, and biliary tract cancers including requirements for HER2 positivity, age >=18, oncologist involvement, concomitant trastuzumab (and capecitabine for breast), prior therapy requirements, RAS/BRAF/dMMR/MSI-H/POLE-POLD1 considerations, and dosing limits (<=600 mg/day and <=4 tablets/day) or guideline-supported alternatives.

Initial therapy updates — Initial therapy criteria updated with newly approved colorectal indication and redirection language.

Initial therapy criteria updated with newly approved colorectal indication and redirection language.

Initial colorectal indication: RT4 update added criteria for the newly FDA-approved colorectal indication and updated Appendix B with NCCN examples of fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens; see colorectal initial criteria for specific requirements.

Continuation Therapy Criteria

Continuation Therapy — Criteria required to continue tucatinib

Criteria required to continue tucatinib

Continuation therapy: Member has been on Tucatinib for at least 30 days via Centene benefit or has documentation of current use; member is responding to therapy; any requested dose increase must not exceed 600 mg per day and 4 tablets per day unless supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).

Approval duration — Revised approval duration for Commercial line of business.

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

Revision recorded 01.20.22; P&T 05.22

Step Therapy / Prior Treatment Requirements

Requirement	Details
Prior use or failure of specified prior therapies
As listed in diagnosis-specific criteria (e.g., colorectal cancer: progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens per NCCN examples; breast and biliary tract criteria reference prior systemic HER2-directed therapies where applicable).

Coverage-label	Requirement
Anti-HER2 regimen failure prior to tucatinib
Failure of one or more anti-HER2 based regimens is required for redirection in HER2-positive disease per policy updates (3Q 2022); see Appendix B for NCCN examples of systemic HER2 therapies.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization required. Regimen (including trastuzumab and capecitabine when applicable) and dosing must meet policy criteria and medical necessity documentation.

Prior authorization may be required for trastuzumab and capecitabine when used in combination with Tukysa.
Prior authorization may be required for combination therapy for all indications.

Documentation Required

Required Supporting Documentation

Provider must submit documentation (such as office chart notes, lab results, pathology reports, molecular testing results, or other clinical information) supporting that the member has met all approval criteria.

Include documentation of HER2 status and any required biomarker results (e.g., RAS, BRAF, dMMR/MSI-H, POLE/POLD1 when applicable).
Submit prior-line treatment history and rationale if off-label dosing or regimen is requested.

Coding & Quantity Limits

Maximum daily dose

Maximum daily dose600 mg/day

Dosing regimen (typical)300 mg PO BID

Maximum tablets per day4 tablets/day (policy limit)

tucatinib — dosing summary

Tucatinib maximum daily dose600 mg/day

Typical dosing regimen300 mg PO BID (2 doses of 300 mg)

Tablet count limitUp to 4 tablets per day per policy dosing limit

Site of Care

Note

No site restriction specified

No site‑of‑care restriction is specified in this section of the policy; the policy does not limit administration to a particular infusion center or alternate site.

Site of care section states no site restriction specified.

Prior Authorization

Combination therapy may require prior authorization (site‑of‑care note)

Prior authorization may be required for combination therapy across all indications when tucatinib is used with other agents; verify PA requirements for combination regimens when submitting requests.

Policy notes added in 3Q 2024 that prior authorization may be required for combination therapy for all indications.

Definitions

dMMR/MSI-H

AbbreviationdMMR/MSI-H

Definitiondeficient mismatch repair/microsatellite instability-high

Use in policyReferenced in colorectal cancer criteria for checkpoint inhibitor therapy eligibility

HER2

AbbreviationHER2

Definitionhuman epidermal growth factor receptor 2

RelevanceRequired positive tumor status for tucatinib coverage in breast, colorectal, and biliary tract cancer criteria

Background

Tucatinib (Tukysa) is a HER2‑directed tyrosine kinase inhibitor indicated in combination with trastuzumab and capecitabine for the treatment of advanced unresectable or metastatic HER2‑positive breast cancer, including patients with brain metastases, after prior anti‑HER2 regimens. The policy also includes the FDA‑accelerated colorectal indication in combination with trastuzumab and NCCN‑supported off‑label biliary tract cancer criteria; dosing limits for tucatinib are capped at a maximum of 600 mg/day (typical dosing 300 mg PO BID).

Revision History

05.23.24annual_review

Added POLE/POLD1 mutation option for colorectal cancer when ineligible for or progressed on checkpoint inhibitor immunotherapy; added off-label criteria for NCCN-supported biliary tract cancers; added note that prior authorization may be required for combination therapy for all indications.

03.08.23rt_update

RT4: Added criteria for newly FDA‑approved colorectal cancer indication and updated Appendix B with NCCN examples of fluoropyrimidine-, oxaliplatin-, and irinotecan‑based regimens.

04.14.23annual_review

Per NCCN recommendations, added requirement for checkpoint inhibitor immunotherapy for dMMR/MSI‑H colorectal cancer.

OpenPayer

Clinical Policy: Tucatinib (Tukysa)

Coverage Criteria

Initial Therapy

Continuation Therapy Criteria

Step Therapy / Prior Treatment Requirements

Provider Actions and Requirements

Coding & Quantity Limits

Site of Care

Definitions

Background

Revision History