Blue Cross Blue Shield TN Prior Auth Coverage Update

Prior Authorization Requirements and Documentation

Prior Authorization

General prior authorization requirement

Prior authorization is required for the specialty drugs listed in this policy; most agents list coverage duration as "Plan Year," and some agents require specific prerequisite therapy before approval.

Note

Coverage setting may affect PA

Determine the expected coverage setting when submitting requests: some IV antifungals and other agents may be adjudicated under Medicare Part B rather than Part D depending on the drug, indication, and site of administration — provide setting/use details so coverage routing can be determined.

Prior Authorization

CALQUENCE prior authorization

Submit a prior authorization for CALQUENCE for all FDA‑approved and specified medically‑accepted indications; for marginal zone lymphoma document the drug is being used for relapsed, refractory, or progressive disease.

Prior Authorization

COMETRIQ prior authorization

For COMETRIQ used in NSCLC, prior authorization requires documentation that the disease is RET rearrangement–positive.

Prior Authorization

COPIKTRA prior authorization

Prior authorization for COPIKTRA requires documentation that the patient has relapsed or refractory disease for the listed T‑cell and related lymphomas; hepatosplenic T‑cell lymphoma requires refractory disease.

Prior Authorization

Prior authorization required for listed agents

Many specialty agents in the document require prior authorization; check each drug entry for its required medical information and indication‑specific criteria when submitting requests.

Prior Authorization

GLP-1 agonists — PA requirement and exclusions

GLP‑1 receptor agonists (MOUNJARO, OZEMPIC, RYBELSUS, TRULICITY) require PA for T2DM and are excluded when prescribed for weight loss only; submit documentation confirming T2DM diagnosis or qualifying laboratory values.

Provide medical records or lab evidence (A1c ≥6.5% OR OGTT 2‑hr PG ≥200 mg/dL OR FPG ≥126 mg/dL OR random PG ≥200 mg/dL with hyperglycemia symptoms).

Prior Authorization

Age-dependent prior authorization

Some PA rules vary by patient age; many high‑risk medication PA requirements apply for patients 65 years and older — ensure age‑specific criteria and documented prescriber risk assessment are provided for older adults.

PA often does not apply for patients under 65 for listed high‑risk med groups; for patients ≥65 provide risk assessment and documentation that benefits outweigh risks.

Prior Authorization

Specialty/oncology PA requirements

Oncology and other specialty agents routinely require prior authorization with documentation of diagnosis, prior therapies, and biomarker/mutation status as applicable — review the drug’s required medical information before submission.

Prior Authorization

PA groups and requirements

Prior authorization is defined and enforced by PA groups in this policy; for drugs listed under a PA group follow the group‑specific required medical information and indication rules (examples: INREBIC, INQOVI).

Prior Authorization

Selected drug PA highlights

Some drugs have unique PA highlights — for example, LEQEMBI requires confirmed amyloid‑beta pathology by PET or lumbar puncture and is for maintenance after at least 18 months of IV lecanemab; other agents list prerequisite therapy flags.

LEQEMBI: confirmed amyloid beta pathology and prior ≥18 months IV lecanemab documented.

Prior Authorization

PROVIDER ACTIONS (general PA requirement across many groups)

Providers must submit prior authorization requests for the listed drug groups and include the drug‑specific required medical information; coverage is generally limited to FDA‑approved and some medically‑accepted indications.

Prior Authorization

Prior authorization and prerequisite therapy summary

Verify prerequisite therapy fields before requesting PA: some indications require documented trials/failures of specified therapies (step therapy) and many agents list coverage duration as Plan Year unless otherwise noted.

If prerequisite therapy is required (per‑drug), include documentation of trials, failures, intolerance, or contraindications.

Prior Authorization

Oncology prior authorization highlights

Oncology agents frequently require documentation of prior lines of therapy or specific biomarker/mutation status (for example, RUBRACA requires BRCA mutation and prior androgen‑receptor therapy and taxane chemotherapy for mCRPC).

Prior Authorization

Prior authorization required for listed specialty drugs

Prior authorization is required for the specialty drugs listed in the policy; follow each drug’s required medical information when submitting requests (see per‑drug entries for exact documentation).

Prior Authorization

Prior authorization required

Prior authorization is required for the listed specialty medications and typically applies to all FDA‑approved indications and some medically‑accepted indications; include indication‑specific documentation.

Prior Authorization

Prior authorization with combination and biomarker requirements

For certain oncology agents, PA requires documentation that the drug will be used in combination with specified agents and that required genomic alterations are present (combination and biomarker requirements must be shown).

Example: TRUQAP — document PIK3CA/AKT/PTEN alterations and planned combination with fulvestrant when applicable.

Prior Authorization

Prior authorization required

Many specialty drugs require prior authorization and will be reviewed against the indication‑specific criteria (e.g., FLT3 mutation, PAH hemodynamics, NTRK fusion status) — include requisite test results and clinical context.

Note

Coverage duration

Most agents list coverage duration as "Plan Year" unless otherwise specified; verify the per‑drug coverage duration (examples: VOQUEZNA 14 days, some HCV agents use guideline‑based durations).

Prior Authorization

Prior authorization required (drug list segment)

This segment of the drug list requires prior authorization for the named agents; follow each entry’s required documentation (mutation status, prior therapy, standard scales, timing relative to chemo) when submitting PA requests.

Step Therapy

Line/combination therapy requirements

Some oncology agents have explicit line‑of‑therapy or combination requirements — include documentation of prior lines or that the requested use is in the indicated line/combination (see BRAFTOVI, BALVERSA examples).

BRAFTOVI: used with cetuximab or panitumumab for BRAF V600E colorectal cancer (combination required).
BALVERSA: tumor with susceptible FGFR3 alteration and used as subsequent therapy.

Step Therapy

Biologic step therapy requirements

Many biologics require prior inadequate response, intolerance, or contraindication to specified agents (e.g., methotrexate, phototherapy, listed biologics) for new starts in rheumatologic and dermatologic indications.

Document prior trials/failures or contraindications to the named agents per indication.

Documentation Required

Provider action summary for rheumatologic and dermatologic indications

For rheumatologic and dermatologic indications, providers must document trials of specified conventional therapies or phototherapy and show inadequate response, intolerance, or contraindication before biologics will be approved.

Step Therapy

Therapy trials required for certain indications

Certain indications require trials of specified alternative therapies before approval (for example, amitriptyline for depression requires trials of two alternative antidepressants); include trial details in the PA request.

Step Therapy

JAKAFI prerequisite therapy

For JAKAFI in polycythemia vera, document inadequate response, intolerance, or resistance to hydroxyurea before approval; include any additional required prior therapy information.

Step Therapy

IPF prior therapy requirement

For idiopathic pulmonary fibrosis agents (e.g., JASCAYD), document intolerance or contraindication to alternative agents (nintedanib or pirfenidone) prior to approval for new starts.

Step Therapy

PROVIDER ACTIONS (other prior trial requirements)

Some drugs require prior trials or failure of alternative therapies or diagnostic confirmation steps (examples include modafinil, OPIPZA); include relevant trial and diagnostic documentation in the PA.

Step Therapy

Step therapy requirements

Multiple entries enforce step therapy: document trials of specified generic and/or brand products and provide evidence of inadequate response, intolerance, or contraindication as required.

Step Therapy

PROVIDER ACTIONS (prior treatment trials examples)

Several agents require prior treatment trials and/or failures (for example, SCEMBLIX requires prior imatinib/dasatinib/nilotinib in many CML settings); include prior therapy chronology and outcomes.

Step Therapy

Step therapy / prior treatment requirements

For many indications (rheumatology, psoriasis, biologics), include documentation of prior inadequate response, intolerance, or contraindication to methotrexate and/or prior biologic/targeted synthetic DMARDs when required.

Denial Risk

Failure of prior therapies

Prior authorization approvals commonly require documentation that the patient failed or was intolerant to prior standard therapies (e.g., XELJANZ requires prior TNF inhibitor for certain indications).

Step Therapy

Prerequisite therapy/step therapy (drug-specific)

Many drug‑specific entries list prerequisite therapy or step therapy requirements — ensure the PA includes evidence of prior therapy trials, failures, intolerances, or contraindications as specified per drug.

Documentation Required

Platelet counts and prior therapy (ALVAIZ)

For ALVAIZ (avatrombopag) requests, include documented platelet counts meeting initiation or continuation thresholds and prior therapy response/intolerance as specified for ITP, HCV‑associated thrombocytopenia, or severe aplastic anemia.

ITP new starts: untransfused platelet <30,000/mcL OR 30,000–50,000/mcL with symptomatic bleeding or bleeding risk.
ITP continuation: current platelet ≤200,000/mcL OR >200,000 to ≤400,000/mcL with dosing adjustment.

Documentation Required

Genetic testing and disease status (AUGTYRO)

For AUGTYRO and other molecularly targeted agents, provide genetic testing results documenting ROS1 or NTRK gene fusion positivity (and disease stage/status such as recurrent/advanced/metastatic) when required.

Documentation Required

PROVIDER ACTIONS (COTELLIC combination requirement)

For COTELLIC requests in CNS cancers, document tumor BRAF V600E activating mutation positivity and that COTELLIC will be used in combination with vemurafenib per the criteria.

Documentation Required

PROVIDER ACTIONS (CRESEMBA oral route and prior therapy)

For CRESEMBA, indicate oral route of administration and, for invasive aspergillosis or certain candidiasis in HIV, document prior inadequate response/intolerance/contraindication to voriconazole.

Documentation Required

PROVIDER ACTIONS (DAURISMO combination and age/comorbidity requirements)

For DAURISMO in AML, document that the drug will be used in combination with cytarabine and that the patient is ≥75 years or has comorbidities precluding intensive chemotherapy per the coverage conditions.

Documentation Required

PROVIDER ACTIONS (ERLOTINIB EGFR documentation)

For ERLOTINIB in NSCLC, include documentation that disease is recurrent/advanced/metastatic and that the patient has a sensitizing EGFR mutation.

Documentation Required

PROVIDER ACTIONS (GLP-1 documentation requirement)

For GLP‑1 agonist requests for diabetes, include medical records or labs meeting diagnostic thresholds and document that the agent is not being used for weight loss only and that there are no contraindicated concomitant GLP‑1/DPP‑4 agents.

Documentation Required

PROVIDER ACTIONS (HARVONI HCV documentation list)

For HCV agents (e.g., HARVONI, MAVYRET), submit HCV RNA prior to starting, planned regimen, genotype, prior treatment history, cirrhosis status, HIV coinfection status, resistance‑associated substitutions where applicable, and transplant status.

Documentation Required

Prescriber risk assessment and counseling

Prescribers must document a risk assessment and counseling for selected high‑risk medications demonstrating that benefits outweigh risks and that risks/side effects were discussed with the patient.

Documentation Required

Required oncology diagnostic information

For oncology targeted therapies, include required diagnostic information such as biomarker/mutation status (e.g., HER2, EGFR, BRAF, FLT3) and disease stage (recurrent/advanced/metastatic) as specified per agent.

Documentation Required

NSCLC EGFR documentation

For NSCLC EGFR‑targeted agents (gefinitib/erlotinib), document that disease is recurrent, advanced, or metastatic and that a sensitizing EGFR mutation is present.

Documentation Required

IVIG documentation

For IVIG requests, include serum IgG thresholds or transplant timing as applicable (e.g., IgG <500 mg/dL for CLL; within 100 days post BMT/HSCT or IgG <400 mg/dL for BMT/HSCT; pediatric HIV thresholds).

Documentation Required

LORBRENA documentation

For LORBRENA in recurrent/advanced/metastatic NSCLC, document ALK‑positive disease or ROS1 rearrangement and any required prior therapy history per the drug entry.

Documentation Required

PROVIDER ACTIONS (HCV MAVYRET documentation)

For MAVYRET HCV requests, include HCV RNA prior to treatment, planned regimen, genotype, prior treatment history, cirrhosis status, HIV coinfection status, resistance‑associated substitutions where applicable, and transplant status as required.

Documentation Required

PHESGO documentation note

For PHESGO requests include documentation as indicated; for HER2‑positive recurrent breast cancer include indication specifics where applicable.

Documentation Required

Severe aplastic anemia documentation

For severe aplastic anemia, document use with standard immunosuppressive therapy or prior insufficient response to immunosuppressive therapy and, for adults, prior eltrombopag intolerance when required.

Documentation Required

PROVIDER ACTIONS (tumor mutation/biomarker documentation examples)

When tumor mutation/biomarker status is required (e.g., MET exon 14 skipping, BRAF V600E, EGFR sensitizing mutation, PDGFRA exon 18), include laboratory or genomic testing results in the PA submission.

Documentation Required

PROVIDER ACTIONS (hematologic/oncology mutation testing)

For hematologic/oncology indications that require specific mutation testing (e.g., Philadelphia chromosome/BCR‑ABL, T315I, F317L), include the diagnostic test results and mutation assay details with the request.

Documentation Required

Testosterone laboratory and consent documentation

For testosterone therapy initial approval, include at least two confirmed low morning serum total testosterone concentrations per reference laboratory or guideline; for gender dysphoria document informed decision to engage in hormone therapy.

Provide two morning total testosterone measurements before starting therapy.

Documentation Required

PAH hemodynamic confirmation

For PAH therapies (WHO Group 1 new starts), include right heart catheterization results documenting pretreatment mean PAP >20 mmHg, PCWP ≤15 mmHg, and PVR >2 Wood units.

Documentation Required

Tumor biomarker documentation

Tumor biomarker status must be documented for HER2‑targeted and other biomarker‑driven agents (e.g., HER2‑amplified/positive, RAS/BRAF wild‑type for colorectal) as specified in the drug entry.

Documentation Required

Diagnostic and biomarker documentation

Provide diagnostic confirmation and biomarker/mutation test results where required (e.g., FLT3‑ITD for VANFLYTA, TTR mutation or technetium scintigraphy/biopsy for ATTR‑CM) when requesting coverage.

Documentation Required

Infectious disease documentation examples

For infectious disease therapies (e.g., VOQUEZNA, VOSEVI, MAVYRET), include microbiologic confirmation (HCV RNA) and genotype/treatment history per AASLD‑IDSA guidance.

Documentation Required

Sleep disorder treatment documentation

For sleep disorder agents (cataplexy, narcolepsy, idiopathic hypersomnia), initial requests require diagnostic confirmation by sleep lab evaluation; continuation requests must document clinical benefit (reduced daytime sleepiness or cataplexy episodes).

Documentation Required

Psoriasis severity and prior therapy documentation

For psoriasis biologics (e.g., YESINTEK), document disease severity and prior therapy: crucial body area involvement OR ≥10% BSA OR ≥3% BSA plus prior inadequate response/intolerance to phototherapy or specified systemic agents for new starts.

Documentation Required

PPD standardized rating scale requirement

For ZURZUVAE (postpartum depression), confirm diagnosis using a standardized rating scale (e.g., HDRS, EPDS, PHQ‑9, MADRS) and include the scale results with the PA request.

Documentation Required

G-CSF timing and indication documentation

For ZARXIO given with chemotherapy, document cancer type (solid tumor or non‑myeloid cancer), chemotherapy exposure, and ensure administration is at least 24 hours after chemotherapy when used for prophylaxis/treatment of febrile neutropenia.

Confirm administration timing: ≥24 hours after chemotherapy.

Denial Risk

Hemodynamics required for PAH (denial risk)

Requests for PAH therapies may be denied if right heart catheterization confirmation and the required hemodynamic thresholds (mean PAP >20 mmHg, PCWP ≤15 mmHg, PVR >2 Wood units) are not provided for new starts.

Denial Risk

Molecular confirmation required (example AYVAKIT)

For molecularly targeted agents, lack of documented molecular confirmation (e.g., FIP1L1‑PDGFRA or PDGFRA D842V for AYVAKIT) and failure/resistance to required prior therapies may result in denial.

Denial Risk

PROVIDER ACTIONS (COMETRIQ RET requirement reminder)

Reminder: COMETRIQ for NSCLC will be reviewed only when the disease is RET rearrangement–positive; absence of documented RET rearrangement may result in non‑approval.

Denial Risk

PROVIDER ACTIONS (COPIKTRA relapsed/refractory limitation)

For COPIKTRA, requests limited to relapsed or refractory disease for listed lymphomas — approvals may be denied if relapsed/refractory status is not documented.

Denial Risk

Part A/B vs Part D coverage denial risk mention

Coverage under Part D will be denied when the medication administration is covered under Medicare Part A or Part B for the individual; document setting and whether the medication is incident to services to determine appropriate coverage routing.

Denial Risk

High-risk medication age-based PA risk

Requests for high‑risk medications for patients aged 65 and older may be denied if required PA conditions (FDA‑approved diagnosis or compendia indication, prescriber risk assessment, documented counseling) are not met.

Denial Risk

Part A/B coverage denial risk

Coverage under Part D will be denied if coverage is available under Part A or Part B for the medication as prescribed and administered for the individual — confirm whether the drug will be billed under Part A/B.

Denial Risk

PROVIDER ACTIONS (ITP prior therapy requirement / denial risk)

For ITP new starts (chronic or persistent), lack of documented inadequate response or intolerance to corticosteroids or immunoglobulins may result in non‑approval.

Denial Risk

PROVIDER ACTIONS (oncology prior therapy denial risk example)

For mCRPC RUBRACA requests, absence of documentation of prior androgen receptor‑directed therapy and prior taxane chemotherapy (or documentation patient is unfit for chemotherapy) may trigger denial.

Denial Risk

PROVIDER ACTIONS (TADALAFIL exclusion for ED)

TADALAFIL for BPH is excluded when the indication is erectile dysfunction; do not submit PA for ED under the BPH criterion.

Denial Risk

PROVIDER ACTIONS (oncology prior therapy and mutation documentation summary)

Many oncology agents require documented prior therapies or mutation status (e.g., CML/Ph+ diagnosis and mutation testing); absence of required prior therapy documentation or mutation results may trigger denial.

Denial Risk

Part D coverage exclusion when covered under Part A/B

If a medication is otherwise payable under Part A or Part B for the individual, Part D coverage will be denied — confirm coverage pathway and include setting details in the PA submission.

Denial Risk

Prior lines required

Requests may be denied when prerequisite therapy or prior lines of therapy are not met (for example, agents that require prior specific therapies or multiple prior lines such as XPOVIO); include prior therapy history.

Denial Risk

PAH confirmation requirements

For PAH therapies, failure to provide right heart catheterization confirmation and the required hemodynamic thresholds for new starts (mean PAP >20 mmHg, PCWP ≤15 mmHg, PVR >2 Wood units) may lead to denial.

Denial Risk

Molecular marker documentation required

Requests for BRAF‑targeted therapy (e.g., ZELBORAF) require documentation of BRAF V600E (CNS tumors) or BRAF V600 activating mutations (melanoma); absence of documented BRAF mutation may lead to non‑approval.

Note

Required Molecular / Biomarker Testing

inv-217: BRAF V600E

BRAF V600ERequired tumor BRAF V600E mutation for multiple indications (e.g., colorectal BRAF V600E, CNS tumors, melanoma)

Evidence sourcePolicy lists BRAF V600E as required biomarker for agents such as BRAFTOVI, COTELLIC, ZELBORAF

Activating V600 mutationsV600E or V600K noted as activating BRAF V600 variants in policy entries

inv-218: FGFR3

FGFR3 alterationsSusceptible FGFR3 genetic alterations required for BALVERSA in urothelial carcinoma

Line requirementUse specified as subsequent therapy for locally advanced/recurrent/metastatic disease per BALVERSA entry

Test documentationTumor genetic testing demonstrating FGFR3 alteration required in required medical information

inv-219: ROS1, NTRK

ROS1 gene fusionROS1-positive required for ROS1-targeted indications (e.g., ROS1-positive NSCLC)

NTRK gene fusionNTRK fusion-positive required for NTRK-targeted indications (e.g., NTRK fusion-positive solid tumors); tumor must lack acquired resistance mutation

Agent examplesROZLYTREK, VITRAKVI, AUGTYRO entries reference ROS1/NTRK fusion requirements

inv-220: FIP1L1-PDGFRA; PDGFRA D842V

FIP1L1–PDGFRA rearrangementRequired for AYVAKIT in myeloid/lymphoid neoplasms with eosinophilia

PDGFRA D842V mutationPresence of PDGFRA D842V mutation specified for AYVAKIT (and PDGFRA exon 18 contexts)

Imatinib resistanceAYVAKIT requires disease resistant to imatinib in specified indications

inv-221: BRAF V600

BRAF V600 (V600E/V600K)BRAF V600 activating mutations (V600E or V600K) required for COTELLIC/RAF-targeted uses

Tumor typesUsed in melanoma, CNS cancers, and other solid tumors per agent-specific entries

Combination requirementCOTELLIC often required to be used in combination with vemurafenib per CNS/melanoma entries

inv-222: RET rearrangements

RET rearrangements/fusionsRET rearrangement or RET fusion–positive tumor required for RET-targeted therapy (e.g., COMETRIQ, GAVRETO)

NSCLC contextFor NSCLC, disease must be recurrent/advanced/metastatic and RET fusion/rearrangement–positive

DocumentationRequired medical information includes testing demonstrating RET alteration

inv-223: EGFR sensitizing mutation

EGFR sensitizing mutationSensitizing EGFR mutation–positive disease required for EGFR-targeted agents (e.g., erlotinib, gefitinib, osimertinib)

NSCLC disease stateDisease typically must be recurrent, advanced, metastatic or specified adjuvant setting per agent

Prior TKI intolerance contextSome agents require prior intolerance or contraindication to specific EGFR TKIs as documented

inv-224: RET fusion / RET rearrangement

RET fusion / RET rearrangementTumor must be RET fusion-positive or RET rearrangement-positive for RET-directed therapies (e.g., GAVRETO, COMETRIQ) in NSCLC

Required disease stateRecurrent, advanced, or metastatic disease for NSCLC entries

Testing requirementDocumentation of RET fusion/rearrangement required in required medical information

inv-225: PIK3CA mutation

PIK3CA mutationPIK3CA mutation required for certain indications (e.g., everolimus in specified histiocytoses; TRUQAP PIK3CA/AKT/PTEN contexts)

Breast cancer contextPIK3CA alterations referenced for targeted therapy combinations in HR-positive breast cancer entries

DocumentationTumor genetic testing showing PIK3CA alteration required where specified

inv-226: HER2 (ERBB2) mutation or amplification

HER2 (ERBB2) mutation or amplificationHER2 mutation or HER2 amplification/overexpression required for HER2-targeted therapies across multiple tumor types

Colorectal specificsFor colorectal cancer, tumor must be HER2-amplified AND RAS/BRAF wild-type and used in specified combinations

Combination therapyMany HER2 indications require combination with pertuzumab, tucatinib, or lapatinib per criteria

inv-227: EGFR mutation-positive

EGFR mutation-positiveEGFR mutation–positive disease required for select agents (e.g., GILOTRIF) after intolerance to other EGFR TKIs or in specific settings

Prior-TKI intoleranceSome entries require intolerance/contraindication to erlotinib/gefitinib/osimertinib before alternative EGFR TKIs

NSCLC settingsIncludes recurrent/advanced/metastatic disease and brain/leptomeningeal metastases where specified

inv-228: HER2 (ERBB2)

HER2 (ERBB2)HER2-amplified or HER2-positive tumor required for many HER2-directed agents across tumor types

Testing and combinationDocumentation of HER2 status and use in combination regimens required for colorectal, hepatobiliary, endometrial indications

RAS/BRAF wild-type requirementFor HER2-amplified colorectal cancer additional requirement of RAS and BRAF wild-type is specified

inv-229: EGFR (sensitizing mutation)

EGFR (sensitizing mutation)Sensitizing EGFR mutation–positive tumors required for gefitinib and similar EGFR TKIs

Disease stateRecurrent, advanced, or metastatic NSCLC typically specified

DocumentationRequired medical information must document sensitizing EGFR mutation status

inv-230: PIK3CA

PIK3CAPIK3CA mutation required for specific targeted therapy indications (e.g., in HR-positive, HER2-negative breast cancer combinations)

Combination requirementOften specified as necessary in combination with fulvestrant or other agents per drug entry

Testing documentationTumor PIK3CA testing required where noted in required medical information

inv-231: EGFR

EGFREGFR sensitizing mutation–positive disease required for EGFR-targeted therapy coverage

Indication examplesGefitinib, erlotinib, osimertinib and related EGFR TKIs reference EGFR mutation status in NSCLC entries

Disease-stage requirementRecurrent/advanced/metastatic disease commonly specified

inv-232: KRAS G12C

KRAS G12C mutationKRAS G12C mutation–positive required for LUMAKRAS and other KRAS-targeted agents

Tumor typesNSCLC is primary listed indication; off-label tumor types listed include pancreatic, colorectal, ampullary adenocarcinoma

DocumentationGenetic testing confirming KRAS G12C required per policy entries

inv-233: HER2 (colorectal RAS/BRAF wild-type)

HER2 (colorectal, RAS/BRAF WT)HER2-positive or HER2-amplified disease required for HER2-targeted therapy in colorectal cancer with RAS/BRAF wild-type status

Combination regimenRequested HER2-directed agent often required in combination with pertuzumab, tucatinib, or lapatinib

Prior HER2 inhibitorSome entries require patient not previously treated with a HER2 inhibitor or specify metachronous metastases

inv-234: KRAS G12C (duplicate)

KRAS G12C (duplicate)KRAS G12C mutation–positive required for coverage of KRAS-targeted agents such as LUMAKRAS

Off-label usesPolicy lists off-label tumor types where KRAS G12C positivity may support use

Required documentationLaboratory confirmation of KRAS G12C mutation required

inv-235: BRCA1/2 (germline)

BRCA1/2 (germline)Germline BRCA1 or BRCA2 deleterious mutation required for certain LYNPARZA and RUBRACA indications (e.g., mCRPC, recurrent/metastatic breast)

Indication examplesRUBRACA for mCRPC requires deleterious BRCA mutation (germline and/or somatic) and prior therapies per criteria

Testing requirementDocumentation of BRCA mutation status required in required medical information

inv-236: HER2 amplification/overexpression

HER2 amplification/overexpressionHER2 amplification or overexpression required for HER2-targeted therapy across multiple tumor types

Colorectal specificColorectal HER2-amplified disease also requires RAS/BRAF wild-type per policy

CombinationCombining with trastuzumab/pertuzumab/tucatinib/lapatinib specified by indication

inv-237: BRAF V600 / BRAF fusion/rearrangement

BRAF V600 (V600E/V600K) and fusionsBRAF V600 activating mutations or BRAF fusion/rearrangement required for multiple indications (melanoma, CNS, solid tumors)

Agent examplesTAFINLAR, vemurafenib (ZELBORAF) and combination regimens referenced for BRAF V600 alterations

Tumor typesMelanoma, NSCLC (V600E), thyroid carcinoma, histiocytoses, hairy cell leukemia, and select CNS tumors

inv-238: BRCA (deleterious germline/somatic)

BRCA (deleterious germline and/or somatic)Deleterious BRCA mutation (germline and/or somatic) required for PARP inhibitor indications (e.g., RUBRACA, LYNPARZA) in prostate, ovarian, breast settings

Prior therapy contextFor mCRPC RUBRACA requires prior androgen receptor–directed therapy and taxane chemotherapy (or documented not fit for chemo)

DocumentationTesting and documentation of BRCA-altered disease required in required medical information

inv-239: FLT3

FLT3 mutation (including ITD)FLT3 mutation-positive (FLT3-ITD) required for certain AML therapies (e.g., VANFLYTA, RYDAPT)

Use contextsRequired for induction, re-induction, consolidation, maintenance, or relapsed/refractory AML per agent

Testing documentationLaboratory confirmation of FLT3 (including ITD) required in required medical information

inv-240: ROS1 / NTRK

ROS1ROS1-positive tumor required for ROS1-targeted indications (e.g., ROZLYTREK)

NTRK fusionNTRK gene fusion presence (without acquired resistance mutation) required for NTRK-targeted therapy (e.g., VITRAKVI, ROZLYTREK)

Tumor testingDocumentation of ROS1 or NTRK fusion required where specified

inv-241: MET exon 14 skipping

MET exon 14 skippingMET exon 14 skipping mutation required for TABRECTA/TEPMETKO/XALKORI MET-related indications in NSCLC

NSCLC contextTumor must be MET exon 14 skipping–positive for recurrent/advanced/metastatic NSCLC entries

DocumentationMolecular testing confirming MET exon 14 skipping required in required medical information

inv-242: BRAF V600 (V600E or V600K)

BRAF V600 (V600E or V600K)Activating BRAF V600E or V600K mutation required for various BRAF-targeted indications

Combination with MEK inhibitorOften used in combination with trametinib/binimetinib per tumor type and indication

Tumor typesMelanoma, NSCLC (V600E), thyroid carcinoma, histiocytoses, hairy cell leukemia, and others

inv-243: EGFR sensitizing mutation

EGFR sensitizing mutationEGFR sensitizing mutation positivity required for osimertinib and other EGFR-directed agents in NSCLC

Indication settingsApplies to metastatic/advanced, adjuvant, and brain/leptomeningeal metastases settings per drug entries

DocumentationGenetic test confirming EGFR sensitizing mutation required in required medical information

inv-244: PDGFRA exon 18

PDGFRA exon 18PDGFRA exon 18 mutation (including D842V) required for certain GIST indications and AYVAKIT/related agents

GIST contextPresence of PDGFRA exon 18 mutation supports use in residual, unresectable, recurrent/metastatic GIST per entries

Testing requirementMolecular testing documentation required where specified

inv-245: BCR-ABL / Philadelphia chromosome

BCR-ABL / Philadelphia chromosomeDetection of Philadelphia chromosome or BCR-ABL gene required for CML and Ph+ ALL indications

Mutation testing contextAdditional mutation testing (e.g., T315I) required when TKI resistance is present per agent entry

Therapy sequencingPresence of Ph chromosome used to guide TKI selection and prior therapy requirements

inv-246: HER2 (amplified/positive)

HER2 (amplified/positive)HER2-amplified or HER2-positive disease required for HER2-directed agents across tumor types

Combination and tumor-specific rulesColorectal requires RAS/BRAF wild-type and combination regimens; hepatobiliary/endometrial require specified partners

DocumentationPathology or molecular testing showing HER2 amplification/overexpression required

inv-247: PIK3CA/AKT/PTEN

PIK3CA/AKT/PTEN alterationsPresence of one or more PIK3CA/AKT/PTEN alterations required for some targeted therapy approvals (e.g., TRUQAP)

Breast cancer contextUsed to select patients for combination endocrine-targeted regimens where specified

DocumentationMolecular testing demonstrating alterations required in required medical information

inv-248: IDH1

IDH1 mutationDocumented susceptible IDH1 mutation required for IDH1-directed therapy (e.g., TIBSOVO) in indicated settings

Tumor typesIncluded for AML and certain CNS tumors per policy entries

TestingMolecular confirmation of IDH1 mutation required in required medical information

inv-249: FLT3-ITD

FLT3‑ITD positiveFLT3 internal tandem duplication (ITD) positivity required for FLT3-directed AML therapies

Use contextsRequired for induction, re-induction, consolidation, maintenance, or relapsed/refractory AML per agent entries

DocumentationLaboratory confirmation of FLT3‑ITD required in required medical information

inv-250: FLT3 (including ITD)

FLT3 (including ITD)FLT3 mutation-positive (including ITD) required for specified AML therapies

Agent examplesVANFLYTA, RYDAPT, others reference FLT3 positivity as requirement

Testing documentationMolecular testing confirming FLT3 mutation required per required medical information

inv-251: HR/HER2 status

HR/HER2 statusHormone receptor and HER2 tumor status required to determine appropriate targeted/combination therapy in breast cancer indications

Combination rulesSelection of combinations (e.g., exemestane, fulvestrant) depends on HR/HER2 context per policy

DocumentationPathology/report demonstrating HR and HER2 status required

inv-252: NTRK fusion

NTRK fusionPresence of NTRK gene fusion (without acquired resistance mutation) required for NTRK-targeted therapy (e.g., VITRAKVI)

Tumor‑agnostic useNTRK fusion–positive solid tumors eligible when no acquired resistance mutation present

DocumentationMolecular testing confirming NTRK fusion required

inv-253: TTR gene mutation / technetium scintigraphy

TTR gene mutation / technetium scintigraphyVariant ATTR-CM: positive TTR gene mutation OR positive technetium‑labeled scintigraphy with light‑chain amyloidosis ruled out

Cardiac imaging confirmationCardiac involvement confirmed by echocardiography or cardiac MRI (e.g., septal thickness >12 mm) or technetium scintigraphy

Exclusion of AL amyloidosisSystemic light‑chain amyloidosis must be ruled out via absence of monoclonal proteins (serum/urine immunofixation, free light chains)

inv-254: BRAF V600E or V600 activating mutation

BRAF V600E or other V600 activating mutationBRAF V600E or other V600 activating mutation required for vemurafenib/related BRAF‑targeted uses

Tumor typesCNS cancers, melanoma, NSCLC, histiocytoses, hairy cell leukemia and certain solid tumors referenced

Combination optionsMay be used alone or combined with cobimetinib/trametinib depending on indication

inv-255: BRCA-altered disease

BRCA‑altered diseaseBRCA‑altered disease (deleterious germline and/or somatic) required for multiple PARP inhibitor indications

Indication examplesRUBRACA, LYNPARZA entries reference BRCA‑altered disease for ovarian, breast, prostate and other contexts

DocumentationGenetic testing confirming BRCA alteration required in required medical information

Covered Combination Regimens and Regimen Constraints

Regimen	Indication / Notes	Coverage stance
COTELLIC + vemurafenib	COTELLIC used for tumors positive for BRAF V600 (e.g., V600E/V600K); for CNS cancers the tumor must be BRAF V600E and COTELLIC is used in combination with vemurafenib; for melanoma COTELLIC is used with vemurafenib for unresectable/limited resectable/metastatic disease.	Covered

Regimen	Indication / Notes	Coverage stance
DAURISMO + cytarabine	For acute myeloid leukemia (AML): DAURISMO must be used in combination with cytarabine and the patient is ≥75 years or has comorbidities precluding intensive chemotherapy; used as treatment/post-induction/consolidation as specified.	Covered

Regimen	Indication / Notes	Coverage stance
Requested HER2-directed agent + pertuzumab/tucatinib/lapatinib	For HER2-amplified colorectal cancer (RAS and BRAF wild-type) the requested HER2-directed agent must be used in combination with pertuzumab, tucatinib, or lapatinib; similar combination requirements apply for hepatobiliary and endometrial HER2-positive disease per agent-specific notes.	Covered

Regimen	Indication / Notes	Coverage stance
Everolimus + exemestane / fulvestrant / tamoxifen	For HR-positive, HER2-negative breast cancer (recurrent, unresectable, advanced, or metastatic): everolimus is prescribed in combination with exemestane, fulvestrant, or tamoxifen for subsequent treatment.	Covered

Regimen	Indication / Notes	Coverage stance
Agent-specific targeted regimens (examples)	Targeted agents are covered when tumor biomarker/mutation status and disease-stage criteria are met — e.g., gefitinib for sensitizing EGFR mutation–positive recurrent/advanced/metastatic NSCLC; HER2-directed agents for HER2-mutated or HER2-amplified NSCLC per required documentation.	Covered

Regimen	Indication / Notes	Coverage stance
KANJINTI + pertuzumab/tucatinib/lapatinib	For HER2-amplified colorectal cancer and other listed HER2-positive indications, KANJINTI may be used in combination with pertuzumab, tucatinib, or lapatinib per the specific indication text; prior intolerable adverse event to Trazimera requirements apply for trastuzumab biosimilars per agent entries.	Covered

Regimen	Indication / Notes	Coverage stance
Requested HER2-directed agent + pertuzumab or tucatinib	For HER2-positive hepatobiliary carcinoma and other tumor types, the requested HER2-directed agent is covered when used in combination with pertuzumab or tucatinib as specified and HER2 positivity/amplification documented.	Covered

Regimen	Indication / Notes	Coverage stance
OGIVRI + pertuzumab/tucatinib/lapatinib	OGIVRI and related HER2-targeted agents are covered for HER2-amplified colorectal cancer when used in combination with pertuzumab, tucatinib, or lapatinib and RAS/BRAF wild-type disease is documented; other HER2 indications have similar combination and biomarker requirements.	Covered

Regimen	Indication / Notes	Coverage stance
BRAF inhibitor (vemurafenib, dabrafenib, encorafenib) — single agent or combination	BRAF inhibitors are covered for BRAF V600–mutant tumors per tumor type: e.g., melanoma, CNS tumors, NSCLC, histiocytoses. Use as single agent or in combination with MEK inhibitors (cobimetinib, trametinib, dabrafenib) per the listed indications and required documentation of BRAF V600 mutation.	Covered

Regimen	Indication / Notes	Coverage stance
TAFINLAR ± trametinib	TAFINLAR (vemurafenib-related entries) and related BRAF inhibitors used with or without trametinib are covered for BRAF V600–mutated cancers (melanoma, NSCLC V600E, thyroid carcinoma not amenable to RAI, histiocytoses, hairy cell leukemia, solid tumors) per FDA-approved indications.	Covered

Regimen	Indication / Notes	Coverage stance
Osimertinib (TAGRISSO)	Osimertinib is covered per FDA-approved indications for EGFR mutation–positive NSCLC in multiple settings, including recurrent/advanced/metastatic disease and brain/leptomeningeal metastases; documentation of sensitizing EGFR mutation required.	Covered

Regimen	Indication / Notes	Coverage stance
HER2 inhibitor + pertuzumab/tucatinib/lapatinib (for colorectal cancer)	HER2 inhibitors are covered for HER2-amplified colorectal cancer when RAS and BRAF are wild-type and the HER2-directed agent is used in combination with pertuzumab, tucatinib, or lapatinib as specified; required tumor biomarker documentation applies.	Covered

Regimen	Indication / Notes	Coverage stance
VANFLYTA (gilteritinib) for FLT3-ITD AML — induction / re-induction / consolidation / maintenance	VANFLYTA is covered for AML that is FLT3-ITD positive for induction, re-induction, consolidation, or maintenance per the indication and required biomarker documentation.	Covered

Regimen	Indication / Notes	Coverage stance
Venetoclax + dexamethasone ± daratumumab or proteasome inhibitor	For multiple myeloma with t(11;14), venetoclax is covered when used in combination with dexamethasone and with daratumumab or a proteasome inhibitor as specified in the required regimen criteria.	Covered

Regimen	Indication / Notes	Coverage stance
crizotinib (XALKORI) per FDA-approved or medically-accepted indications	Crizotinib is covered for ROS1-positive NSCLC or MET-altered NSCLC per listed conditions; prior therapy requirements apply (e.g., inadequate response/intolerance to specified ALK inhibitors for ALK-positive NSCLC when indicated).	covered_with_criteria

Regimen	Indication / Notes	Coverage stance
Vemurafenib ± cobimetinib	Vemurafenib (ZELBORAF) is covered for tumors positive for BRAF V600 mutations — CNS tumors (BRAF V600E) in combination with cobimetinib or per pediatric indications, melanoma (V600 activating mutations) as single agent or with cobimetinib, and NSCLC with BRAF V600E for recurrent/advanced/metastatic disease — per listed indications.	Covered

Definitions and Abbreviations

inv-178: PAH confirmation

PAH confirmation by RHCRight heart catheterization confirming PAH required for WHO Group 1 PAH new starts

mPAP threshold> 20 mmHg

PCWP and PVR thresholdsPCWP ≤ 15 mmHg; PVR > 2 Wood units

inv-179: APR/IPR platelet response definitions

APR (adequate platelet response)> 50,000/mcL

IPR (inadequate platelet response)< 50,000/mcL

Platelet response definitions — policy useAPR/IPR used to determine continuation and reauthorization criteria for ITP and severe AA

inv-180: BRAF V600 activating mutation (COTELLIC)

BRAF V600 activating mutation (COTELLIC context)Tumor positive for BRAF V600 activating mutation (e.g., V600E or V600K) required when COTELLIC used with vemurafenib

Combination requirementCOTELLIC must be used in combination with vemurafenib for CNS/melanoma indications per policy

Tumor testingMolecular test confirming BRAF V600 activating mutation required

inv-181: Sensitizing EGFR mutation-positive

Sensitizing EGFR mutation-positive (definition)EGFR activating mutations that predict response to EGFR TKIs; required for gefitinib/erlotinib/ osimertinib coverage in NSCLC

Clinical contextDisease must be recurrent, advanced, or metastatic when specified in NSCLC entries

DocumentationMolecular testing confirming sensitizing EGFR mutation required

inv-182: RET fusion-positive / RET rearrangement-positive

RET fusion-positive / RET rearrangement-positiveTumor RET fusion or RET rearrangement positivity required for RET-targeted therapy coverage in NSCLC and other specified tumors

Disease stateRecurrent, advanced, or metastatic disease commonly specified for NSCLC RET indications

Required documentationMolecular testing confirming RET fusion/rearrangement required

inv-183: PIK3CA mutation definition

PIK3CA mutation — definitionPIK3CA mutation presence required for certain indications such as selected histiocytic disorders and breast cancer combinations

Indication examplesPolicy references PIK3CA for everolimus in ECD/LCH/Rosai‑Dorfman and TRUQAP contexts

DocumentationTumor molecular testing demonstrating PIK3CA alteration required where specified

inv-184: Sensitizing mutation (generic)

Sensitizing mutation (generic)Tumor genetic alteration (e.g., EGFR sensitizing mutation, HER2 mutation) that predicts response to targeted oncology therapies

UsageRequired to qualify for specific targeted agents per drug entries

DocumentationGenetic/molecular testing results required per 'Required Medical Information' entries

inv-185: Sensitizing EGFR mutation-positive (duplicate/definition)

Sensitizing EGFR mutation-positive (duplicate)EGFR activating mutations required for EGFR TKI coverage in NSCLC

Clinical requirementRecurrent, advanced, or metastatic disease commonly specified

TestingConfirmatory molecular testing required

inv-186: KRAS G12C mutation-positive

KRAS G12C mutation-positive (definition)Presence of KRAS G12C oncogenic mutation required for coverage of agents like LUMAKRAS

Tumor examplesNSCLC is primary; off‑label tumor types listed in policy may be considered per agent-specific criteria

DocumentationMolecular test confirming KRAS G12C required

inv-187: KRAS G12C-positive (duplicate)

KRAS G12C-positive (duplicate)Tumors confirmed to harbor KRAS G12C mutation for which agents like LUMAKRAS are indicated

Disease stateRecurrent, locally advanced, or metastatic disease specified for NSCLC indications

Off-label contextsPolicy lists several off-label tumor types supported by KRAS G12C positivity per agent

inv-188: BRCA 1/2-germline mutated

BRCA 1/2 — germline mutatedPresence of germline BRCA1 or BRCA2 mutation required for certain LYNPARZA indications (e.g., recurrent/metastatic breast cancer)

Therapy contextsAlso used to qualify patients for PARP inhibitor maintenance and other indications per drug-specific rules

DocumentationGermline BRCA testing results required where specified

inv-189: HER2-amplified/HER2-positive

HER2-amplified / HER2-positiveTumors with HER2 overexpression or amplification required for HER2-targeted therapies and specified combinations

Colorectal specificsColorectal HER2 amplification additionally requires RAS/BRAF wild-type per policy

DocumentationPathology/molecular confirmation of HER2 status required

inv-190: APR / IPR (duplicate definition)

APR / IPR definitionsAPR = adequate platelet response (>50,000/mcL); IPR = inadequate platelet response (<50,000/mcL)

Use in continuation criteriaAPR/IPR thresholds used to determine reauthorization and dosing adjustments for ITP and severe AA

Policy referenceDefinitions appear in ALVAIZ and eltrombopag entries across the policy

inv-191: mCRPC definition

mCRPC (definition) — BRCA contextMetastatic castration-resistant prostate cancer with deleterious BRCA mutation (germline and/or somatic) as specified for RUBRACA

Prior therapy requirementRUBRACA mCRPC requires prior androgen receptor–directed therapy and prior taxane chemotherapy or documentation patient not fit for chemo

Combination requirementRUBRACA in mCRPC used in combination with GnRH analog or after bilateral orchiectomy per entry

inv-192: MET exon 14 skipping mutation

MET exon 14 skipping mutation (definition)Driver MET exon 14 skipping mutation required for TABRECTA/TEPMETKO in recurrent/advanced/metastatic NSCLC

Testing/documentationMolecular test confirming MET exon 14 skipping required in required medical information

Clinical contextSpecified for recurrent/advanced/metastatic disease per policy entries

inv-193: BRAF V600E/K mutation

BRAF V600E/K mutationActivating BRAF V600E or V600K mutation required for TAFINLAR and related BRAF-targeted uses

Tumor typesMelanoma, NSCLC (V600E), thyroid carcinoma, histiocytoses, hairy cell leukemia, solid tumors where indicated

Combination useOften paired with trametinib/binimetinib depending on indication

inv-194: High FRAX fracture probability

High FRAX definition10‑year major osteoporotic fracture ≥ 20% OR hip fracture ≥ 3%

Use with T-scoreHigh FRAX may qualify patients with T-score between -2.5 and -1 for certain osteoporosis therapies

Glucocorticoid adjustmentIf prednisone >7.5 mg/day multiply FRAX major by 1.15 and hip by 1.2

inv-195: PAH confirmation (detailed)

PAH confirmation — detailedRight heart catheterization confirming PAH with pretreatment mPAP >20 mmHg, PCWP ≤15 mmHg, PVR >2 Wood units required for WHO Group 1 PAH new starts

Denial riskLack of RHC confirmation or missing hemodynamic thresholds may trigger denial

DocumentationSubmit RHC report with pretreatment hemodynamics as part of required medical information

inv-196: ATTR-CM diagnostic confirmation

ATTR‑CM diagnostic confirmationCardiac involvement confirmed by imaging or technetium scintigraphy AND diagnosis confirmed by biopsy or positive scintigraphy with AL amyloidosis ruled out; variant disease requires TTR gene mutation

Documentation examplesEchocardiography/cardiac MRI criteria (e.g., septal thickness), technetium‑labeled scintigraphy, biopsy, and absence of monoclonal proteins

ContinuationContinuation requires demonstration of benefit (e.g., slowing clinical decline)

inv-197: BRAF V600 mutation (short)

BRAF V600 mutation (short)BRAF V600 activating mutation required for various BRAF-targeted indications

Variants notedV600E and V600K examples cited in policy

Tumor testingMolecular confirmation required per required medical information

inv-198: ZARXIO timing requirement

ZARXIO timing requirementIf administered with chemotherapy, give at least 24 hours after chemotherapy to avoid interfering with cytotoxic effect

Indication contextUsed for prophylaxis/treatment of chemotherapy‑induced febrile neutropenia in patients with solid tumors or non‑myeloid cancers

DocumentationRequired medical information includes timing relative to chemotherapy per policy

OpenPayer

Prior Authorization Criteria for Specialty and Oncology Drugs

Coverage Criteria by Agent / Indication

Identifiers, Thresholds, and Key Clinical Values

Prior Authorization Requirements and Documentation

Line of Therapy Designations and Requirements

Required Molecular / Biomarker Testing

Covered Combination Regimens and Regimen Constraints

Policy Background and Scope

Definitions and Abbreviations