Centene cabozantinib Coverage Policy Update

Coverage Criteria

Initial Therapy, Renal Cell Carcinoma

Covered when ALL of the following are met

RCC initial approval: 1) Request is for Cabometyx; 2) Diagnosis of relapsed or stage IV (unresectable or metastatic) renal cell carcinoma (RCC); 3) Prescribed by or in consultation with an oncologist; 4) Age ≥ 18 years; 5) For Cabometyx request, member must use cabozantinib when available unless contraindicated or clinically significant adverse effects; 6) Request does not exceed health plan-approved quantity limit, if applicable; 7) Request meets one of the following (a, b, c, or d): a) For monotherapy, dose does not exceed both: i) 60 mg per day; ii) 1 tablet per day; b) For use in combination with Opdivo or Opdivo Qvantig, dose does not exceed both: i) 40 mg per day; ii) 1 tablet per day; c) Documentation that member is concurrently taking a strong CYP3A4 inducer and dose does not exceed both: i) 80 mg per day; ii) 2 tablets per day; d) 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, Hepatocellular Carcinoma

Covered when ALL of the following are met

HCC initial approval: 1) Request is for Cabometyx; 2) Diagnosis of hepatocellular carcinoma (HCC); 3) Prescribed by or in consultation with an oncologist; 4) Age ≥ 18 years; 5) Prescribed as subsequent-line therapy; 6) Prescribed as single-agent therapy; 7) Confirmation of Child-Pugh class A status; 8) For Cabometyx request, member must use cabozantinib when available unless contraindicated or clinically significant adverse effects; 9) Request does not exceed health plan-approved quantity limit, if applicable; 10) Request meets one of the following (a, b, or c): a) Dose does not exceed both: i) 60 mg per day; ii) 1 tablet per day; b) Documentation that member is concurrently taking a strong CYP3A4 inducer and dose does not exceed both: i) 80 mg per day; ii) 2 tablets per day; c) 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, Thyroid Carcinoma

Covered when ALL of the following are met

Thyroid carcinoma initial approval: 1) Diagnosis of one of the following: a) Recurrent, unresectable, progressive, or metastatic medullary thyroid carcinoma (MTC); or b) Locally advanced, unresectable, or metastatic differentiated thyroid carcinoma (DTC) (including follicular, oncocytic, or papillary histologies); 2) Prescribed by or in consultation with an oncologist; 3) If MTC, request is for Cometriq; if DTC, request is for Cabometyx; 4) Age: for Cabometyx (DTC) ≥ 12 years; for Cometriq (MTC) ≥ 18 years; 5) Prescribed as single-agent therapy; 6) For DTC: failure of lenvatinib (Lenvima) and/or sorafenib unless contraindicated or clinically significant adverse effects; 7) For follicular and papillary thyroid carcinoma: disease refractory to radioactive iodine therapy; 8) For Cabometyx or Cometriq requests, member must use cabozantinib when available unless contraindicated or clinically significant adverse effects; 9) Request does not exceed health plan-approved quantity limit, if applicable; 10) Request meets one of the following dosing options: a) For Cabometyx: i) weight ≥ 40 kg — dose does not exceed both 60 mg/day and 1 tablet/day; ii) weight < 40 kg — dose does not exceed both 40 mg/day and 1 tablet/day; iii) if concurrently taking a strong CYP3A4 inducer — dose does not exceed both 80 mg/day and 2 tablets/day; b) For Cometriq: i) dose does not exceed both 140 mg/day and 4 capsules/day; ii) if concurrently taking a strong CYP3A4 inducer — dose does not exceed both 180 mg/day and 3 capsules/day; c) 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, Neuroendocrine Tumors

Covered when ALL of the following are met

NET initial approval: 1) Request is for Cabometyx; 2) Diagnosis of pancreatic neuroendocrine tumor (pNET) or extra-pancreatic neuroendocrine tumor (epNET) (including but not limited to GI tract, lung/thymus, well-differentiated grade 3 disease, adrenocortical carcinoma, pheochromocytoma, paraganglioma); 3) Disease is unresectable, recurrent, locally advanced, or metastatic; 4) Prescribed by or in consultation with an oncologist; 5) Age ≥ 12 years; 6) Prescribed as either: a) single-agent; or b) for GI tract pNET/epNET, in combination with Sandostatin LAR or lanreotide; 7) For Cabometyx request, member must use cabozantinib when available unless contraindicated or clinically significant adverse effects; 8) Request does not exceed health plan-approved quantity limit, if applicable; 9) Request meets one of the following dosing options: a) weight ≥ 40 kg — dose does not exceed both 60 mg/day and 1 tablet/day; b) weight < 40 kg — dose does not exceed both 40 mg/day and 1 tablet/day; c) if concurrently taking a strong CYP3A4 inducer — dose does not exceed both 80 mg/day and 2 tablets/day; d) 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, NSCLC RET+ (off-label)

Covered when ALL of the following are met

NSCLC RET rearrangement (off-label): 1) Diagnosis of non-small cell lung cancer (NSCLC) that is recurrent, advanced, or metastatic and positive for RET gene rearrangement; 2) Prescribed by or in consultation with an oncologist; 3) Age ≥ 18 years; 4) Prescribed as single-agent therapy; 5) Prescribed as subsequent therapy following progression on selpercatinib (Gavreto) or pralsetinib (Retevmo); 6) For Cabometyx or Cometriq requests, member must use cabozantinib when available unless contraindicated or clinically significant adverse effects; 7) Request does not exceed health plan-approved quantity limit, if applicable; 8) Dose is within 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

Initial Therapy, Additional NCCN Uses

Covered when ALL of the following are met

Additional NCCN recommended uses: 1) Request is for Cabometyx; 2) Diagnosis is one of: a) Gastrointestinal stromal tumor (GIST) that is gross residual (R2 resection), unresectable, tumor rupture, recurrent, or metastatic; b) Recurrent or metastatic endometrial carcinoma; c) Bone cancers: Ewing sarcoma, osteosarcoma, mesenchymal chondrosarcoma, dedifferentiated chondrosarcoma, or high-grade undifferentiated pleomorphic sarcoma; d) Soft tissue sarcomas (e.g., alveolar soft part sarcoma, extraskeletal myxoid chondrosarcoma, epithelioid hemangioendothelioma, pleomorphic rhabdomyosarcoma, retroperitoneal/intra-abdominal STS, extremity/body wall, head/neck STS); 3) Prescribed by or in consultation with an oncologist; 4) Age ≥ 18 years; 5) Prescribed as single-agent therapy; 6) For GIST, endometrial carcinoma, and bone cancer: prescribed as second-line or subsequent therapy; 7) For Cabometyx requests, member must use cabozantinib when available unless contraindicated or clinically significant adverse effects; 8) Request does not exceed health plan-approved quantity limit, if applicable; 9) Dose is within 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

Continued Therapy

Covered when ALL of the following are met

Continued therapy general criteria: 1) Member is currently receiving medication via Centene benefit, or documentation supports current receipt of Cabometyx or Cometriq for a covered indication for at least 30 days; 2) Member is responding positively to therapy; 3) For Cabometyx or Cometriq requests, member must use cabozantinib when available unless contraindicated or clinically significant adverse effects; 4) Request does not exceed health plan-approved quantity limit, if applicable; 5) If request is for a dose increase, request meets one of the following: a) For Cabometyx: i) For monotherapy, dose does not exceed both 60 mg/day and 1 tablet/day; ii) For use in combination with Opdivo or Opdivo Qvantig, dose does not exceed both 40 mg/day and 1 tablet/day; iii) Documentation that member is concurrently taking a strong CYP3A4 inducer and dose does not exceed both 80 mg/day and 2 tablets/day; b) For Cometriq: i) Dose does not exceed both 140 mg/day and 4 capsules/day; ii) Documentation that member is concurrently taking a strong CYP3A4 inducer and dose does not exceed both 180 mg/day and 3 capsules/day; c) New 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

Coverage criteria by indication

Coverage is provided with specified criteria and dosing per indication; refer to indication‑specific requirements and NCCN-aligned updates.

General dosing and formulation: Cabometyx tablets (20, 40, 60 mg) dosing: typical monotherapy 60 mg PO QD for HCC/RCC/DTC/pNET/epNET; RCC combination therapy 40 mg PO QD with nivolumab (Opdivo) or Opdivo Qvantig; reduce the daily Cabometyx dose by 20 mg for strong CYP3A4 inhibitors and increase by 20 mg for strong CYP3A4 inducers; Cometriq (capsules) for MTC: 140 mg PO QD with adjustments of ±40 mg for strong CYP3A4 modifiers; maximum Cabometyx listed as 80 mg/day and Cometriq maximum as 180 mg/day in dosing guidance.

DTC specific: For differentiated thyroid carcinoma (DTC), coverage aligned to NCCN: Cabometyx is the allowed cabozantinib formulation (Cometriq is not used for DTC); disease qualifiers reflect locally advanced, unresectable, or metastatic disease and radioactive iodine status is 'refractory'.

HCC specific: For hepatocellular carcinoma (HCC), disease qualifiers were removed per NCCN and coverage includes single-agent subsequent-line use; alternative first-line systemic therapy regimens are listed in Appendix B.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider submits sufficient documentation of efficacy and safety in accordance with applicable off‑label use policies (see CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or evidence of coverage documents.

Non‑FDA approved indications not described in this policy are excluded from coverage unless the request is supported by adequate documentation per the referenced off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) or there is other documented evidence of coverage demonstrating efficacy and safety for the requested use.

Requests for uses that are not listed in this policy and that lack supporting evidence as required by off‑label use policies may be considered not medically necessary and denied; providers should include clinical documentation demonstrating efficacy and safety consistent with the referenced off‑label policies to support coverage consideration.

Covered Regimens and Dosing

Regimen	Indication / Notes	Daily Dose Limit
{"text":"Cabometyx (cabozantinib) tablets — monotherapy","status":""},{"text":"Renal cell carcinoma; also used for HCC, DTC, pNET, epNET per indication-specific criteria. Prescriber must be oncologist or in consultation; member must use cabozantinib product when available unless contraindicated.","status":""},{"text":"60 mg per day; maximum 1 tablet/day for monotherapy","status":""}
{"text":"Cabometyx (cabozantinib) tablets — with nivolumab (Opdivo or Opdivo Qvantig)","status":""},{"text":"Renal cell carcinoma combination therapy (RCC). Eligible per updated 1Q 2026 criteria permitting Opdivo Qvantig combination.","status":""},{"text":"40 mg per day; maximum 1 tablet/day when combined with nivolumab","status":""}
{"text":"Cabometyx (cabozantinib) tablets — concurrent strong CYP3A4 inducer scenario","status":""},{"text":"Applies across indicated uses when documentation shows concurrent strong CYP3A4 inducer (see Appendix D). Prescriber must submit documentation when dose exceeds standard caps.","status":""},{"text":"Up to 80 mg per day; maximum 2 tablets/day when a strong CYP3A4 inducer is present","status":""}

Regimen	Indication / Notes	Daily Dose Limit
{"text":"Cometriq (cabozantinib) capsules — standard dosing","status":""},{"text":"Medullary thyroid carcinoma (MTC). Prescribed by or in consultation with an oncologist; member must use cabozantinib product when available unless contraindicated.","status":""},{"text":"140 mg per day; up to 4 capsules/day","status":""}
{"text":"Cometriq (cabozantinib) capsules — concurrent strong CYP3A4 inducer","status":""},{"text":"If documentation shows concurrent strong CYP3A4 inducer (see Appendix D) and prescriber provides supporting evidence.","status":""},{"text":"Up to 180 mg per day; 3 capsules/day when taking a strong CYP3A4 inducer per policy allowances","status":""}

Regimen	Indication / Notes	Daily Dose Limit
{"text":"Cabometyx (cabozantinib) 40 mg PO QD in combination with nivolumab","status":""},{"text":"Renal cell carcinoma combination therapy with nivolumab (Opdivo). Also allowed with Opdivo Qvantig (nivolumab + hyaluronidase-nvhy) per 1Q 2026 update. Prescriber must document indication and oncologist involvement.","status":""},{"text":"40 mg once daily; maximum 1 tablet/day","status":""}

Regimen	Indication / Notes	Daily Dose Limit
{"text":"Cabometyx (cabozantinib) 60 mg PO QD — typical adult monotherapy","status":""},{"text":"Typical dosing for adult monotherapy across HCC, RCC, DTC, pNET, and epNET where indicated; prescriber must be oncologist or in consultation and requests must meet indication-specific criteria.","status":""},{"text":"60 mg once daily (monotherapy); reduce by 20 mg for strong CYP3A4 inhibitors or increase by 20 mg for strong CYP3A4 inducers as specified","status":""}

Regimen	Indication / Notes	Daily Dose Limit
{"text":"Cometriq (cabozantinib) 140 mg PO QD (capsules)","status":""},{"text":"Standard dosing for medullary thyroid carcinoma (MTC). Prescriber must be oncologist or in consultation; member must use cabozantinib product when available unless contraindicated.","status":""},{"text":"140 mg once daily (4 capsules/day); reduce by 40 mg for strong CYP3A4 inhibitors or increase by 40 mg for strong CYP3A4 inducers per dosing guidance","status":""}

Coding and Dose Limits

HCPCS referencedHCPCS

J8999

Prescription drug, oral, chemotherapeutic, NOS

Cabometyx dosing limits

Maximum daily dose (Cabometyx)80 mg/day

Typical adult monotherapy dose60 mg PO QD (may be adjusted for CYP3A4 modifiers)

RCC combination dose with nivolumab40 mg PO QD

Cometriq dosing limits

Maximum daily dose (Cometriq for MTC)180 mg/day

Standard Cometriq dose for MTC140 mg PO QD (4 capsules/day); adjust ±40 mg for strong CYP3A4 modifiers

Age requirement for Cometriq (MTC)

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization required. Provider must obtain prior authorization and demonstrate that the member meets the indication‑specific criteria (diagnosis, age, line of therapy, specialist involvement, dosing limits, and prior therapies) described in the policy.

Prior authorization required for all indications listed in this policy.
Provider must demonstrate indication‑specific criteria (diagnosis, age, line of therapy, specialist involvement, dosing limits, and prior therapies).

Prior Authorization

Prior Authorization and Approval Duration

Prior authorization approvals have specific durations depending on line of business. Initial approval durations and any recent updates must be confirmed at time of request.

Medicaid/HIM — initial approval: 12 months.
Commercial — initial approval: 12 months or duration of request, whichever is less.

Line of Therapy

subsequent-line

HCC line: Prescribed as subsequent-line therapy for hepatocellular carcinoma (HCC).

second-line

Second-line requirement: For GIST, endometrial carcinoma, and specified bone cancers, cabozantinib is prescribed as second-line or subsequent therapy.

subsequent-line

NSCLC subsequent-line: For RET-positive NSCLC, cabozantinib is prescribed as subsequent therapy following progression on selpercatinib (Gavreto) or pralsetinib (Retevmo).

Biomarker Requirements

Biomarker requirement (NSCLC)

RET gene rearrangement test result requiredPositive

Indication contextRequired for off-label NSCLC RET+ coverage (recurrent, advanced, or metastatic)

Line of therapy requirementPrescribed as subsequent therapy following progression on selpercatinib (Gavreto) or pralsetinib (Retevmo)

Definitions

Cabozantinib (overview)

Drug class and formulationsA kinase inhibitor available as Cabometyx (tablet) and Cometriq (capsule)

Indications summaryIndicated for multiple advanced cancers including RCC, HCC, DTC, pNET, epNET (Cabometyx) and MTC (Cometriq)

Formulation noteCabometyx tablets come in 20/40/60 mg strengths; Cometriq provided as capsules with dosing up to 140 mg/day (standard) or up to policy maximums

Hepatic function requirement

Required hepatic status for HCCChild-Pugh class A

Indication contextConfirmation of Child-Pugh class A required for Cabometyx use in hepatocellular carcinoma

Background

Cabozantinib is an oral kinase inhibitor available as Cabometyx (tablets) and Cometriq (capsules) and is used in multiple malignancies including advanced renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), medullary and differentiated thyroid cancers, and pancreatic and extra‑pancreatic neuroendocrine tumors. Dosing, formulation, and approval status vary by indication and may include combination use (for example, Cabometyx with nivolumab in RCC) or single‑agent regimens; the policy distinguishes product formulations and requires that prescribed regimens be FDA‑approved or recommended by the NCCN compendium.

OpenPayer

Clinical Policy: Cabozantinib (Cabometyx, Cometriq)

Coverage Criteria

Covered Regimens and Dosing

Coding and Dose Limits

Provider Actions and Requirements

Line of Therapy

Biomarker Requirements

Definitions

Background