Prior Auth Protocol

FDA Approved Indications:

Treatment of adult patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib.
Treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic.
Treatment of pediatric and adult patients with tuberous sclerosis complex (TSC) who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.
Treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.
Treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole (Femara^R) or anastrozole (Arimidex^R).

Health Net Approved Indications and Usage Guidelines:

Advanced or metastatic renal cell carcinoma with predominant clear cell histology

Diagnosis of advanced or metastatic renal cell carcinoma with predominant clear cell histology

AND

Failure or clinically significant adverse effects to Sutent^R, Nexavar^R, Votrient, Inlyta, Avastin in combination with Intron-A or Torisel

AND

Failure or clinically significant adverse effects to Opdivo and Cabometyx

Advanced or metastatic renal cell carcinoma (RCC), non-clear cell histology

Diagnosis of advanced or metastatic renal cell carcinoma with non-clear cell histology

Progressive neuroendocrine tumors of pancreatic origin (PNET) that is unresectable, locally advanced or metastatic

Diagnosis of progressive neuroendocrine tumors of pancreatic origin (PNET) that is unresectable, locally advanced or metastatic

Non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic.

Diagnosis of Non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic.

Subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS)

Diagnosis of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS)

AND

Patient is not a candidate for curative surgical resection

Renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery

Diagnosis of renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery

Hormone receptor positive, human epidermal growth factor receptor-2 (HER-2)negative metastatic breast cancer

Diagnosis of hormone receptor positive, human epidermal growth factor receptor-2 negative metastatic breast cancer

AND

Failure or clinically significant adverse effects to a nonsteroidal aromatase inhibitor anastrozole (Arimidex^R) or letrozole (Femara ^R)

AND

In combination with exemestane (Aromasin^R)

Diagnosis of any of the following:

Hodgkins Lymphoma
Soft Tissue Sarcoma- PEComa/Recurrent Angiomyolipoma/Lymphangioleiomyomatosis
Thymomas and Thymic Carcinomas (second line therapy as a single agent)
Waldenstroms Macroglobulinemia (for previously treated disease that does not respond to primary therapy or for progressive or relapsed disease)

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.

General Information:

Reimbursement support (AfiniTRAC^TM program) for healthcare providers and patients is available at 1-888-5AFINITRAC (1-888-523-4648).
Advanced renal cell carcinoma includes relapsed disease or Stage IV and medically or surgically unresectable disease.
Use in metastatic breast cancer in combination with Aromasin(a steroidal aromatase inactivator) after failure of a nonsteroidal aromatase inhibitor (such as Arimidex or Femara) is a category 2A recommendation per NCCN compendium.
Hodgkins Lymphoma, Soft Tissue Sarcoma- PEComa/Recurrent Angiomyolipoma/Lymphangioleiomyomatosis, Thymomas and Thymic Carcinomas (second line therapy as a single agent), Waldenstroms Macroglobulinemia (for previously treated disease that does not respond to primary therapy or for progressive or relapsed disease) are category 2A recommendations per NCCN compendium.
NCCN recommends patients should receive Opdivo^R(nivolumab) and Cabometyx(cabozantinib) over Afinitor for subsequent therapy in renal cell carcinoma, predominant clear cell histology.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
Sutent (sunitinib)	Advanced RCC 50 mg PO QD for 4 weeks followed by 2 weeks off. Advanced PNET: 37.5 mg PO QD Dose increase or reduction of 12.5 mg increments is recommended based on individual safety and tolerability.	Advanced RCC 87.5 mg/day Advanced PNET 62.5 mg/day Treatment continues until no longer clinically beneficial or unacceptable toxicity occurs.
Nexavar (sorafenib)	Advanced RCC 400 mg PO BID Management of adverse reactions may require temporary interruption and/or dose reduction. When dose reduction is necessary, the dose may be decreased to 400 mg PO QD. If additional dose reduction is required, the dose may be reduced to 400 mg PO QOD.	Advanced RCC 800 mg/day Treatment continues until no longer clinically beneficial or unacceptable toxicity occurs.
Torisel^R(temsirolimus)	Advanced RCC 25 mg IV infused over 30-60 minutes once a week.	Advanced RCC 50 mg/week Treatment continues until no longer clinically beneficial or unacceptable toxicity occurs.
Avastin^R(bevacizumab) in combination with Intron A^R(interferon alfa-2b)	Advanced RCC 10 mg/kg IV infused over 60-90 minutes every 2 weeks (in combination with interferon alfa 3 million IU SC/IM 5 times per week up to 36 million IU SC/IM 3 times per week)	Advanced RCC 15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks (in combination with interferon alfa 20 million IU/m²/day IV; 35 million IU/m²/dose SC/IM)
Proleukin^R(aldesleukin, rIL-2)	Advanced RCC 600,000 IU/kg IV Q8 hrs for 14 doses, repeat after a rest period of 9 days	Advanced RCC 600,000 IU/kg IV Q8 hrs; 18 million IU/m²/day IV has been used off-label for RCC
Zanosar^R(streptozocin)	Advanced PNET Daily Dose: 500 mg/m² IV for five consecutive days every six weeks until maximum benefit or until treatment-limiting toxicity is observed. Weekly Dose: 1000 mg/m² IV at weekly intervals for the first two courses (weeks). In subsequent courses, drug doses may be escalated in patients who have not achieved a therapeutic response and who have not experienced significant toxicity with the previous course of treatment.	Advanced PNET 1500 mg/m² IV in a SINGLE dose
Votrient^R(pazopanib)	Advanced RCC 800 mg PO QD	Advanced RCC 800 mg/day Treatment continues until no longer clinically beneficial or until unacceptable toxicity occurs.
Inlyta (axitinib)	Advanced RCC: 5 mg PO BID	Advanced RCC: 10 mg PO BID Treatment continues until no longer clinically beneficial or unacceptable toxicity occurs.
Opdivo (nivolumab)	Advanced RCC: 3 mg/kg IV every 2 weeks	Advanced RCC: 3 mg/kg every 2 weeks
Cometriq (cabozantinib)	Advanced RCC: 60 mg PO QD	Advanced RCC: 60 mg PO QD

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Afinitor	Advanced PNET, N-euroendocrine tumors (NET) of gastrointestinal (GI) or lung origin, Advanced RCC, Hormone Receptor Positive Breast Cancer and Renal Angiomyolipoma with TSC, Hodgkins Lymphoma, Soft Tissue Sarcoma-PEComa/Recurrent Angiomyolipoma/Lymphangioleiomyomatosis, Thymomas and Thymic Carcinomas, Waldenstrom's Macroglobulinemia, stage IIIb (T4 due to multiple lung nodules)-IV low-or intermediate-grade neuroendocrine carcinoma: 10 mg PO QD Management of adverse reactions may require temporary treatment interruption and/or dose reduction to 5 mg PO QD. For patients with Child-Pugh class B hepatic impairment, reduce dose to 5 mg PO QD. If moderate inhibitors of CYP3A4 or P-glycoprotein (PgP) are required, reduce dose to 2.5 mg PO QD. If tolerated, consider increasing to 5 mg PO QD. If strong inducers of CYP3A4 are required, increase dose in 5 mg increments to a maximum of 20 mg PO QD. SEGA: 4.5 mg/m² PO QD; adjust dose to attain trough concentrations of 5-15 ng/mL. Management of adverse reactions may require temporary treatment interruption and/or dose reduction and/or frequency of dosing reduction to every other day. If moderate inhibitors of CYP3A4 or P-glycoprotein (PgP) are required, reduce dose by approximately 50%, or if patient is taking 2.5 mg PO QD, consider alternate day dosing. If strong inducers of CYP3A4 are required, double the Afinitor dose.	Length of benefit

Product Availability:

Tablet: 2.5 mg, 5 mg, 7.5 mg and 10 mg
Tablet for oral suspension: 2 mg, 3 mg, 5 mg

References:

1. Afinitor [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; February 2016.

2. National Comprehensive Cancer Network. Kidney Cancer Version 2.2016. Available at: http://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed February 10, 2016.

3. National Comprehensive Cancer Network. Neuroendocrine Tumors Version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Accessed July 1, 2014.

4. National Comprehensive Cancer Network. Breast Cancer Version 3.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed July 1, 2014.
5. Yao, JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2015 Dec 15. pii: S0140-6736(15)00817-X. doi: 10.1016/S0140-6736(15)00817-X. [Epub ahead of print].