Prior Auth Protocol

FDA Approved Indications:

Treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test.

Health Net Approved Indications and Usage Guidelines:

AND

Positive for the b-Raf serine-threonine kinase (BRAF) V600E mutation detected by an FDA-approved test.

OR

Diagnosis of Non-Small Cell Lung Cancer positive for the BRAF V600E mutation detected by an FDA-approved test

OR

Diagnosis of Hairy Cell Leukemia that is non-responsive to purine analog therapy (e.g., pentostatin, cladribine)

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.
Patients with wild-type BRAF melanoma.

General Information:

Zelboraf can potentiate the activity of the mitogen-activated protein kinase (MAPK) pathway in cells with wild-type BRAF and could accelerate the growth of some tumors with wild-type BRAF.
Dose reductions resulting in a dose below 480 mg twice daily are not recommended.
The current National Comprehensive Cancer Network (NCCN) guideline recommends that the preferred therapy for patients with metastatic melanoma is participation in a clinical trial, even though Zelboraf, Yervoy, and Tafinlar are category 1 recommendations.
Zelboraf is not FDA approved to treat patients with V600K mutations. A study with 10 patients showed a partial response rate of 40 percent. Mekinist is FDA approved to treat V600K mutations.
The cobas^R 4800 BRAF V600E test can only give a positive or negative result for the V600E mutation; it does not test for the other mutation variants.
According to the NCCN, Zelboraf has a category 2A recommendation for Hairy Cell Leukemia as a single-agent in patients with the indication for treatment for progression if non-responsive to purine analog therapy.
According to the NCCN, Zelboraf has a category 2A recommendation for Non-Small Cell Lung Cancer for activity against BRAF V600E mutation in lung cancer.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Yervoy^TM(ipilimumab)	3 mg/kg IV every 3 weeks for 4 doses	Limited to 4 lifetime doses within 16 weeks of the initial dose
dacarbazine (DTIC-Dome^R)	250 mg/m² IV days 1-5 every 3 weeks or 2 to 4.5 mg/kg IV once daily for 10 day repeated every 4 weeks	Dose can vary depending on chemotherapy regimen
cladribine	0.09 mg/kg/day continuous IV infusion for 7 days for 1 cycle	This field intentionally left blank.
Nipent (pentostatin)	4 mg/m² IV every 2 weeks The optimal duration has not been determined; in the absence of unacceptable toxicity, may continue until complete response is achieved or until 2 doses after complete response	Discontinue after 6 months if partial or complete response is not achieved.

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Zelboraf	960 mg PO BID	Length of Benefit

Product Availability:

Zelboraf: 240 mg tablets

References:

Zelboraf [Prescribing information]. South San Francisco, CA: Genentech USA, Inc.; August 2015.
Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011; 364:2507-16.
National Comprehensive Cancer Network (NCCN). Melanoma Version 2.2016; Available at: http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. Accessed January 7, 2016.