Health Net cabozantinib Coverage & Prior Auth

Coverage Criteria for Cabozantinib (Cabometyx, Cometriq)

Initial Therapy — Renal Cell Carcinoma

Covered when ALL of the following are met:

RCC initial criteria: 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 if available unless contraindicated or clinically significant adverse effects are experienced; 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. Monotherapy: dose does not exceed both 60 mg per day and 1 tablet per day; b. Combination with Opdivo or Opdivo Qvantig: dose does not exceed both 40 mg per day and 1 tablet per day; c. Documentation that member is concurrently taking a strong CYP3A4 inducer and dose does not exceed both 80 mg per day and 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.

See policy for Appendix D drug interaction considerations and required supporting evidence.

Initial Therapy — Hepatocellular Carcinoma

Covered when ALL of the following are met:

HCC initial criteria: 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 if available unless contraindicated or clinically significant adverse effects are experienced; 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 60 mg per day and 1 tablet per day; b. Documentation that member is concurrently taking a strong CYP3A4 inducer and dose does not exceed both 80 mg per day and 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.

See policy for Child‑Pugh requirement and Appendix D interactions.

Initial Therapy — Thyroid Carcinoma

Covered when ALL of the following are met:

Thyroid carcinoma initial criteria: 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 [Hurthle cell], or papillary); 2. Prescribed by or in consultation with an oncologist; 3. If MTC, request is for Cometriq; if DTC, request is for Cabometyx; 4. Age criteria: Cabometyx (DTC) age ≥ 12 years; Cometriq (MTC) age ≥ 18 years; 5. Prescribed as single-agent therapy; 6. For DTC: failure of lenvatinib and/or sorafenib unless contraindicated or clinically significant adverse effects are experienced; 7. For follicular and papillary DTC: disease refractory to radioactive iodine therapy; 8. For Cabometyx or Cometriq requests, member must use cabozantinib if available unless contraindicated or clinically significant adverse effects are experienced; 9. Request does not exceed health plan-approved quantity limit, if applicable; 10. Request meets one of the following dose options: a. For Cabometyx: i. Weight ≥ 40 kg: dose does not exceed both 60 mg per day and 1 tablet per day; ii. Weight < 40 kg: dose does not exceed both 40 mg per day and 1 tablet per day; iii. Documentation of concurrent strong CYP3A4 inducer and dose does not exceed both 80 mg per day and 2 tablets per day; b. For Cometriq: i. Dose does not exceed both 140 mg per day and 4 capsules per day; ii. Documentation of concurrent strong CYP3A4 inducer and dose does not exceed both 180 mg per day and 3 capsules per day; c. Dose 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.

Prior authorization may be required; see policy for detailed dosing matrix and pediatric considerations.

Initial Therapy — Neuroendocrine Tumors

Covered when ALL of the following are met:

Neuroendocrine tumors initial criteria: 1. Request is for Cabometyx; 2. Diagnosis of pancreatic neuroendocrine tumor (pNET) or extra‑pancreatic neuroendocrine tumor (epNET) (including specified origins such as gastrointestinal tract, lung/thymus, well‑differentiated grade 3, adrenocortical, 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, for pNET/epNET of the gastrointestinal tract, in combination with Sandostatin LAR (octreotide) or lanreotide; 7. For Cabometyx request, member must use cabozantinib if available unless contraindicated or clinically significant adverse effects are experienced; 8. Request does not exceed health plan-approved quantity limit, if applicable; 9. Request meets one of the following (a, b, c, or d): a. Weight ≥ 40 kg: dose does not exceed both 60 mg per day and 1 tablet per day; b. Weight < 40 kg: dose does not exceed both 40 mg per day and 1 tablet per day; c. Documentation that member is concurrently taking a strong CYP3A4 inducer and dose does not exceed both 80 mg per day and 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.

Combination with somatostatin analogues specified for GI tract NETs; see policy for pediatric weight‑based dosing.

Initial Therapy — NSCLC (RET+)

Covered when ALL of the following are met:

NSCLC RET rearrangement criteria: 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 if available unless contraindicated or clinically significant adverse effects are experienced; 7. Request does not exceed health plan‑approved quantity limit, if applicable; 8. Dose is within FDA maximum limits 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.

Off‑label use restricted to after progression on approved RET inhibitors per NCCN guidance.

Initial Therapy — Additional NCCN recommended uses

Covered when ALL of the following are met:

Additional NCCN off-label indications: 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) Specified soft tissue sarcomas (examples: 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 (for STS monotherapy required); 6. For GIST, endometrial carcinoma, and bone cancer: prescribed as second‑line or subsequent therapy; 7. For Cabometyx requests, member must use cabozantinib if available unless contraindicated or clinically significant adverse effects are experienced; 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.

Off‑label uses limited to NCCN‑recommended diagnoses and specified lines of therapy; see Appendix for examples.

Continued Therapy — All Indications

Covered when ALL of the following are met:

Continued therapy criteria: 1. Member is currently receiving medication via Centene benefit, or documentation supports current receipt of Cabometyx or Cometriq for a covered indication and has received the medication for at least 30 days; 2. Member is responding positively to therapy; 3. For Cabometyx or Cometriq requests, member must use cabozantinib if available unless contraindicated or clinically significant adverse effects are experienced; 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. Monotherapy: dose does not exceed both 60 mg per day and 1 tablet per day; ii. Combination with Opdivo or Opdivo Qvantig: dose does not exceed both 40 mg per day and 1 tablet per day; iii. Documentation that member is concurrently taking a strong CYP3A4 inducer and dose does not exceed both 80 mg per day and 2 tablets per day; b. For Cometriq: i. Dose does not exceed both 140 mg per day and 4 capsules per day; ii. Documentation that member is concurrently taking a strong CYP3A4 inducer and dose does not exceed both 180 mg per day and 3 capsules per 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.

Continued therapy requires ≥30 days of prior use and evidence of clinical benefit.

Covered indications/dosing (selected)

Covered indications and dosing (select examples present in this part of the document):

Cabometyx monotherapy (HCC, RCC, DTC, pNET, epNET): Adults: 60 mg PO once daily; reduce daily dose by 20 mg with strong CYP3A4 inhibitors; increase daily dose by 20 mg with strong CYP3A4 inducers.maximum 80 mg/day

Pediatric weight‑based adjustments apply; see pediatric node.

RCC combination therapy: Cabometyx 40 mg PO once daily when given with nivolumab (Opdivo) or Opdivo Qvantig.

Opdivo Qvantig added as an option per 1Q 2026 review.

Cometriq (MTC): Cometriq 140 mg PO once daily; reduce daily dose by 40 mg with strong CYP3A4 inhibitors; increase daily dose by 40 mg with strong CYP3A4 inducers.maximum 180 mg/day

Cometriq capsules are distinct from Cabometyx tablets and are not interchangeable.

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

Coverage for non‑FDA approved indications not specifically addressed in this policy is excluded unless the use is supported by one of the off‑label use policies cited in this document (CP.CPA.09, HIM.PA.154, CP.PMN.53) or by other applicable evidence of coverage that demonstrates sufficient clinical support for the requested indication.

Use of cabozantinib for indications that are not listed in this policy and that lack adequate off‑label support may be considered not medically necessary under the plan’s no‑coverage or medical necessity policies unless the provider submits acceptable evidence per the referenced off‑label use guidance.

Dosing, Formulations, and Regimens

Regimen	Dose / Daily limit	Formulation / Notes
Cabometyx — monotherapy	60 mg per day; does not exceed 1 tablet per day	Tablet; reduce dose by 20 mg with strong CYP3A4 inhibitors; increase by 20 mg with strong CYP3A4 inducers
Cabometyx — in combination with nivolumab (Opdivo) or Opdivo Qvantig	40 mg per day; does not exceed 1 tablet per day	Tablet; specified as combination regimen for RCC
Cabometyx — concurrent strong CYP3A4 inducer documented	Up to 80 mg per day; does not exceed 2 tablets per day	Dose increase allowed when strong CYP3A4 inducer documented (see Appendix D)
Cometriq (cabozantinib) — medullary thyroid carcinoma	140 mg per day; 4 capsules per day	Capsule formulation; with strong CYP3A4 inducer dose may be increased (up to 180 mg/day per continued therapy section)

Appendix B example regimen	Indication / Context	Notes
Atezolizumab + bevacizumab	Hepatocellular carcinoma (HCC) — listed as alternative therapy in Appendix B	Dosing and regimen vary by source; listed among preferred alternatives
Tremelimumab + durvalumab	HCC — listed as alternative therapy in Appendix B	Regimen details vary; provided as an alternative first‑line systemic option
Durvalumab	HCC — listed as alternative therapy in Appendix B	Listed among therapeutic alternatives; dosing varies
Lenvatinib	HCC and DTC — listed as alternative therapy in Appendix B	Dosing varies by indication (Appendix B provides typical dose ranges)
Sorafenib	HCC and DTC — listed as alternative therapy in Appendix B	Listed as a preferred alternative; dosing varies by indication
Tislelizumab	HCC — listed as alternative therapy in Appendix B	Included in Appendix B examples; dosing varies
Pembrolizumab	HCC — listed as alternative therapy in Appendix B	Included among examples of therapeutic alternatives; dosing varies

Regimen	Dose / Daily limit	Formulation / Notes
Cabometyx with nivolumab (Opdivo)	40 mg PO QD; 1 tablet per day	RCC combination; tablet formulation
Cabometyx with Opdivo Qvantig	40 mg PO QD; 1 tablet per day	Opdivo Qvantig (nivolumab and hyaluronidase-nvhy) listed as alternative to Opdivo per RCC combination criteria

Coding and Dose Limits

HCPCS referencedHCPCS

J8999

Prescription drug, oral, chemotherapeutic, NOS

Daily dose limits — Cabozantinib

Monotherapy (Cabometyx)Maximum 60 mg per day (1 tablet) for monotherapy; dose must not exceed both 60 mg/day and 1 tablet/day.

Combination with nivolumab (Opdivo/Opdivo Qvantig)Maximum 40 mg per day (1 tablet) when used in combination with nivolumab; must not exceed both 40 mg/day and 1 tablet/day.

Concurrent strong CYP3A4 inducerIf concurrently taking a strong CYP3A4 inducer (see Appendix D), Cabometyx may be increased up to 80 mg per day (2 tablets) with documentation; Cometriq allowances differ (see respective section).

Pediatric weight threshold for adult dosing

Pediatric weight threshold for adult dosing>= 40 kg: Patients aged >= 12 years and weighing >= 40 kg receive the adult Cabometyx dose of 60 mg PO QD.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization required. Provider must obtain prior authorization and demonstrate that the member meets all indication-specific criteria (diagnosis, prescriber specialty, age, dosing, and any diagnosis‑specific prior therapy requirements).

Prior authorization is required for Cabometyx and Cometriq per policy CP.PHAR.111.
Provider must document diagnosis, prescriber specialty (e.g., oncologist), age, and dosing aligned with the applicable indication.
Requests may be subject to health plan‑approved quantity limits.

Documentation Required

Documentation and Indication Noncoverage

Provider must submit documentation (e.g., office chart notes, lab results, imaging, pathology, medication history) supporting that the member has met all approval criteria. Failure to provide sufficient documentation or requests for indications not addressed in this policy may result in denial.

Line-of-Therapy Specifications

subsequent-line

HCC subsequent-line: Prescribed as subsequent-line therapy (post‑first‑line) and single‑agent

See HCC initial criteria for Child‑Pugh A requirement.

second-line

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

Off‑label NCCN‑recommended uses only; prescriber must provide supporting evidence.

subsequent-line

NSCLC subsequent-line:

Biomarker and Diagnostic Requirements

RET gene rearrangement — Biomarker requirement

RET gene rearrangement requirementPositive for RET gene rearrangement is required for the NSCLC (RET+) off-label indication; NSCLC must be recurrent, advanced, or metastatic.

Line of therapy restrictionUse is restricted to subsequent therapy following progression on selpercatinib (Gavreto) or pralsetinib (Retevmo).

Prescriber and ageMust be prescribed by or in consultation with an oncologist for patients aged >= 18 years.

Definitions and Terms

Cabozantinib — Drug identity

Compound identityCabozantinib is a kinase inhibitor marketed as Cabometyx and Cometriq.

Indications overviewUsed across multiple advanced malignancies including RCC, HCC, DTC, MTC (Cometriq), pNET, and epNET as specified by indication and age.

FormulationsCabometyx tablets and Cometriq capsules are distinct formulations; dosing and interchangeability differ by product.

Child-Pugh class A — HCC requirement

Child-Pugh class A requirementConfirmation of Child-Pugh class A liver function is required for coverage of Cabometyx for hepatocellular carcinoma (HCC).

Line and therapy typeHCC use is specified as subsequent-line, single-agent therapy with prescriber oncology consultation required.

Background

Cabozantinib is a multi‑kinase inhibitor marketed as Cabometyx and Cometriq with regulatory approvals and guideline-supported uses across several advanced malignancies. It is approved and covered under indication‑specific criteria in this policy for renal cell carcinoma, hepatocellular carcinoma (post‑sorafenib or as specified), differentiated thyroid carcinoma, medullary thyroid carcinoma (Cometriq), and for selected well‑differentiated pancreatic and extra‑pancreatic neuroendocrine tumors in patients meeting age and weight criteria. The agent’s mechanism — inhibition of multiple tyrosine kinases involved in tumor growth, angiogenesis, and metastasis — provides the clinical rationale for use across these tumor types and for certain NCCN‑recommended off‑label indications included in this policy.

Policy Revision History and Material Changes

2025-04-16RT4 update

Added neuroendocrine tumors indication and updated differentiated thyroid carcinoma (DTC) dosing for Cabometyx.

2025-10-231Q2026 annual review (documented)

Removed brain metastases from off-label indications, added RCC combination option with Opdivo Qvantig, revised HCC disease qualifiers and Appendix B regimens, and updated DTC request and radioactive iodine language per NCCN.

2026-02-26P&T approval for 1Q2026 reviewLatest

OpenPayer

Clinical Policy: Cabozantinib (Cabometyx, Cometriq)

Coverage Criteria for Cabozantinib (Cabometyx, Cometriq)

Dosing, Formulations, and Regimens

Coding and Dose Limits

Provider Actions, Prior Authorization, and Documentation

Line-of-Therapy Specifications

Biomarker and Diagnostic Requirements

Definitions and Terms

Background

Policy Revision History and Material Changes