CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Zelboraf (vemurafenib) — Coverage Criteria for Malignant Melanoma

Defines accepted indications, inclusion and exclusion criteria, and utilization management process for Zelboraf (vemurafenib) in treating malignant melanoma for members of Neighborhood Health Plan of Rhode Island; applies to provider medication requests processed by Evolent's UM program.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyZelboraf (vemurafenib) — Coverage Criteria for Malignant Melanoma

Policy CodePolicy N/A

Change TypeRoutine review — no material changes

Effective DateMay 31, 2024

Next Review DateN/A

Key ActionObtain prior authorization from Evolent and document BRAF V600E mutation status and line of therapy.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

BRAF V600ERequired biomarker

First or laterLines allowed

960 / 1920 mgDose limits

240 tabsMax monthly

IMspire1503‑drug combo not supported

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Coverage Criteria for Zelboraf (vemurafenib)

inv-01: Malignant Melanoma - Initial or Continuation Therapy

Covered when ALL of the following are met for malignant melanoma:

Melanoma BRAF V600E coverage: Member has metastatic, recurrent, or unresectable malignant melanoma AND tumor is BRAF V600E mutation positive

Supports first‑line or subsequent line use

Regimen options: Vemurafenib may be used in combination with cobimetinib OR as single‑agent vemurafenib if combination therapy is contraindicated

Three‑drug combination with cobimetinib + vemurafenib + atezolizumab is not supported

inv-02: Continuation Request Exemption

Continuation requests exempt from this policy when ALL of the following are met:

Continuation exemptions: Requested medication was used within the last year AND member has not experienced disease progression and/or no intolerance to the requested medication AND no additional medications are being added to the continuation request

Such continuation requests are exempt from this Evolent policy

Use of Zelboraf (vemurafenib) is excluded when any of the following apply: the member has BRAF V600E negative (wild type) melanoma; dosing exceeds the single dose limit of 960 mg or the daily dose limit of 1,920 mg; treatment would exceed the maximum of 240 tablets per month. Also excluded is disease progression on the same regimen or with another combination of a BRAF inhibitor (for example, encorafenib or dabrafenib) plus a MEK inhibitor (for example, binimetinib or trametinib).

Investigational or off‑label uses of Zelboraf (vemurafenib) that are not supported by sufficient evidence are considered not medically necessary. Sufficient evidence must be consistent with CMS‑recognized compendia or acceptable peer‑reviewed literature and should address whether the patient and cancer characteristics, the regimen administered, and the reported outcomes are adequately represented in the published evidence. Case reports and meeting abstracts without full peer‑reviewed publications generally do not provide adequate support.

The policy defines clinically meaningful outcomes in line with ASCO recommendations (for example, hazard ratio < 0.80 and recommended survival benefit for OS or PFS of at least 3 months) and requires that the experimental design be appropriate to the question being asked; nonrandomized trials with substantial subject numbers may be supportive, but abstracts alone are insufficient.

Permitted and Not-Supported Regimens

Regimen	Indication / Notes	Coverage status
Vemurafenib combined with cobimetinib (Cotellic)
Single‑agent vemurafenib (if combination contraindicated)

Regimen	Rationale / Evidence	Coverage status
Cotellic (cobimetinib) + Zelboraf (vemurafenib) + Tecentriq (atezolizumab)

Dosing Limits and Quantity Constraints

Single and daily dose limits

Single dose limit≤ 960 mg per single dose

Daily dose limit≤ 1,920 mg per day

Maximum monthly quantityMaximum 240 tablets per month (240 mg tablets)

Exclusion for dosing exceedanceRequests exceeding these single, daily, or monthly limits are excluded

Provider Requirements and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization required. Evolent UM Department processes medication requests from network ordering providers; medications not authorized by Evolent may be deemed not approvable and not reimbursable.

Prior authorization required through Evolent UM Dept.
Medications not authorized by Evolent may be deemed not approvable and not reimbursable.

Note

Preferred Regimen Structure

Combination therapy with cobimetinib (Cotellic) plus vemurafenib (Zelboraf) is the preferred regimen for BRAF V600 mutation–positive metastatic, recurrent, or unresectable malignant melanoma. Single‑agent vemurafenib (Zelboraf) is allowed when combination therapy is contraindicated. Three‑drug combinations that include cobimetinib + vemurafenib + atezolizumab (Tecentriq) are not supported.

Preferred: cobimetinib (Cotellic) + vemurafenib (Zelboraf) combination.
Single‑agent vemurafenib allowed if combination contraindicated.

Permitted Lines of Therapy

inv-12: first-line | second-line — Coverage allowed in first or later lines

Line of therapy: Covered as first‑line therapy OR as second‑line/subsequent therapy

Required Biomarker Testing

BRAF V600E

Required biomarkerBRAF V600E mutation positive status is required for covered melanoma indication

Applicable cancer typesMetastatic, recurrent, or unresectable malignant melanoma

Line of therapyCovered for first-line or second-line/subsequent therapy when BRAF V600E positive

Key Definitions

Progression on prior BRAF/MEK therapy

DefinitionDisease progression on the same regimen or with another combination of a BRAF inhibitor and a MEK inhibitor

Examples of BRAF inhibitorsEncorafenib, dabrafenib (listed as examples in exclusion criteria)

Examples of MEK inhibitorsBinimetinib, trametinib (listed as examples in exclusion criteria)

Policy consequenceProgression on prior BRAF/MEK therapy is an exclusion to coverage

Background

Vemurafenib is a BRAF inhibitor indicated for the treatment of unresectable or metastatic malignant melanoma harboring BRAF V600 mutations. It may be used as a single agent or in combination with a MEK inhibitor (for example, cobimetinib) depending on clinical appropriateness; however, certain three‑drug combinations evaluated in trials are not supported by this policy.

Revision History

2024-05-31effective_dateLatest

Policy effective date listed as May 31, 2024.

2024-05-08approval_date

Policy approval date recorded as May 8, 2024.

2023-03-08committee_review

Committee reviewed the policy on March 8, 2023 (one of multiple historical review dates).