UnitedHealthcare Zelboraf Prior Auth Coverage

Coverage Criteria

Indication-specific initial and reauthorization criteria

Covered when the specified diagnosis and biomarker/clinical conditions are met

Pediatric under 19: Patient is less than 19 years of age

Auto-authorization for 12 months

Melanoma (initial): Diagnosis of unresectable or metastatic melanoma AND patient is positive for BRAF V600 mutation

Authorization will be issued for 12 months

Melanoma (reauthorization): No evidence of progressive disease while on Zelboraf therapy

Authorization will be issued for 12 months

CNS cancers (initial): Either (a) metastatic brain lesions with Zelboraf active against the primary tumor (melanoma) OR (b) diagnosis of glioma with incomplete resection/biopsy or surgically inaccessible location or recurrent/progressive disease; AND cancer is positive for BRAF V600E mutation; AND used in combination with Cotellic (cobimetinib)

Authorization will be issued for 12 months

CNS cancers (reauthorization): No evidence of progressive disease while on Zelboraf therapy

Authorization will be issued for 12 months

Hairy cell leukemia: Diagnosis of hairy cell leukemia

Authorization will be issued for 12 months; reauthorization requires no progressive disease

Non-small cell lung cancer (NSCLC): Diagnosis of NSCLC AND disease that is metastatic, advanced, or recurrent AND cancer is positive for BRAF V600E mutation

Reauthorization requires no evidence of progressive disease while on therapy

Erdheim-Chester disease or Langerhans cell histiocytosis: Diagnosis of Erdheim-Chester disease OR Langerhans cell histiocytosis AND cancer is positive for BRAF V600 mutation

Reauthorization requires no evidence of progressive disease while on therapy

Thyroid carcinomas (follicular, oncocytic, papillary): Diagnosis of follicular, oncocytic, or papillary carcinoma AND unresectable locoregional recurrent, metastatic, or persistent disease AND symptomatic or progressive disease AND disease refractory to radioactive iodine AND cancer is positive for BRAF V600 mutation

Authorization will be issued for 12 months; reauthorization requires no evidence of progressive disease while on therapy

NCCN recommended regimens

NCCN recognition: Drug recognized by the NCCN Drugs and Biologics Compendium with Category 1, 2A, or 2B for the cancer indication

May guide coverage decisions

Zelboraf (vemurafenib) is not recommended for use in patients with wild-type BRAF melanoma. Coverage and approvals for melanoma indications require documentation of a BRAF V600 or V600E activating mutation as detected by an FDA‑approved test; absence of such documented mutation may result in denial of coverage.

Note that certain recommendations previously referenced from the NCCN Compendium (for example, items related to colon or rectal cancer) were reported as not included in the current version of NCCN guidelines at the time of document updates. State mandates or other jurisdictional requirements may also apply and are noted in the policy references.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Zelboraf (vemurafenib) for members age 19 and older. Members under 19 years of age will auto-process without a coverage review. Approvals are typically issued for up to 12 months.

Prior authorization required except for members <19 (auto-process).
Authorizations (initial and reauthorization) are generally issued for 12 months.

Documentation Required

Diagnosis and Biomarker Documentation Required

Documentation must include the specific diagnosis and laboratory evidence of a qualifying BRAF mutation. Requests lacking documented BRAF V600 (V600E/V600) mutation test results or an appropriate diagnosis may be denied.

Positive BRAF V600/V600E mutation documented (FDA‑approved test or equivalent).
Appropriate diagnosis documented (e.g., unresectable or metastatic melanoma, Erdheim‑Chester disease, CNS cancer with supporting details, thyroid carcinoma subtypes, hairy cell leukemia, NSCLC, LCH, etc.).

Initial Therapy Criteria

Initial therapy rules

Initial authorization criteria vary by indication; most require specific diagnosis and a positive BRAF V600/V600E mutation. CNS cancers require combination with cobimetinib.

General melanoma initial: Diagnosis of unresectable or metastatic melanoma AND patient is positive for BRAF V600 mutation

Authorization will be issued for 12 months

CNS cancer initial: Either (a) metastatic brain lesions with Zelboraf active against the primary melanoma OR (b) glioma with incomplete resection/biopsy or surgically inaccessible location or recurrent/progressive disease; AND cancer is positive for BRAF V600E mutation; AND used in combination with Cotellic (cobimetinib)

Authorization will be issued for 12 months

Thyroid carcinoma initial: Diagnosis of follicular, oncocytic, or papillary carcinoma AND unresectable locoregional recurrent, metastatic, or persistent disease AND symptomatic or progressive disease AND disease refractory to radioactive iodine AND cancer is positive for BRAF V600 mutation

Continuation / Reauthorization Criteria

Reauthorization requirement

Reauthorization

General reauthorization condition: Patient does not show evidence of progressive disease while on Zelboraf therapy

Authorization will be issued for 12 months

Re-authorization

Authorization length: Re-authorization (continuation) will be issued for up to 12 months.

State mandates, federal requirements, and member-specific benefit plans may affect coverage

Step Therapy and Required Combinations

Step	Requirement	Notes
1	For central nervous system (CNS) cancers, vemurafenib (Zelboraf) must be used in combination with cobimetinib (Cotellic)	Applies to initial authorization for metastatic brain lesions from melanoma or glioma meeting listed surgical/clinical criteria; authorization issued for 12 months.

Step	Automation / Decision Logic	Notes
1	Prior authorization decisions may be based on previous claim/medication history, diagnosis codes (ICD-10), and/or claim logic; automated approval and re-approval processes may be used.	Use of automation varies by program and therapeutic class; supply limits may be enforced.

Quantity Limits

vemurafenib (Zelboraf) — quantity/supply limits

Quantity limit statusSupply limits may be enforced for vemurafenib (Zelboraf).

Typical enforcement periodSupply limits and automated processes may be applied at initial approval and reauthorization stages as program rules permit.

Relation to automated approvalsSupply limits may be imposed even when approvals are granted based on prior claim/medication history or claim logic.

Definitions

BRAF V600E mutation — definition and testing requirements

DefinitionBRAF V600E mutation: a specific activating mutation in the BRAF gene required for vemurafenib efficacy in listed indications; detection should be by an FDA‑approved test.

Testing requirementMutation must be detected by an FDA‑approved test (see FDA Companion Diagnostics information referenced in policy).

Indications requiring testingMost covered indications (e.g., unresectable or metastatic melanoma, CNS cancers, NSCLC, Erdheim‑Chester Disease, LCH, certain thyroid carcinomas) require tumor positive for BRAF V600 or V600E mutation as specified per indication.

NCCN Compendium — role in recommended and off‑label uses

Source referencedThe policy references the NCCN Drugs and Biologics Compendium (NCCN Compendium) as a clinical guidance source for recommended regimens and off‑label recommendations.

Background

Vemurafenib (Zelboraf) is a BRAF kinase inhibitor indicated for patients with unresectable or metastatic melanoma harboring the BRAF V600E mutation (detected by an FDA‑approved test) and for Erdheim‑Chester Disease with a BRAF V600 mutation. NCCN guidance recognizes use of vemurafenib in combination with cobimetinib (Cotellic) for certain CNS cancers and for metastatic or unresectable melanoma with BRAF V600 mutations; where combination therapy is contraindicated, single‑agent use is acknowledged. The policy therefore requires documented diagnosis and mutation status to support authorization decisions.

Revision History

2025-03annual_reviewLatest

Annual review updated nomenclature under Thyroid carcinoma from Hurthle cell to oncocytic with no change to clinical intent and updated reference.

2024-03annual_review

Annual review updated background and CNS coverage criteria per NCCN recommendations; updated reference and added state mandate footnote.

2023-03annual_review

OpenPayer

Zelboraf (vemurafenib) prior authorization and coverage criteria

Coverage Criteria

Provider Actions and Requirements

Initial Therapy Criteria

Continuation / Reauthorization Criteria

Step Therapy and Required Combinations

Quantity Limits

Definitions

Background

Revision History