Afinitor, Afinitor Disperz (everolimus)

Afinitor, Afinitor Disperz (everolimus)

Self-Administration – oral

Diagnosis considered for coverage:

• Afinitor (everolimus tablet):
  • Hormone Receptor-Positive, HER2-Negative Breast Cancer - Afinitor is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane, after failure of treatment with letrozole or anastrozole
  • Neuroendocrine Tumors (NET) – 
    • Afinitor is indicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease.
    • Afinitor is indicated for the treatment of adult patients with progressive, well-differentiated, non-functional NET of gastrointestinal (GI) or lung origin with unresectable, locally advanced or metastatic disease.
    • Limitations of Use: Afinitor is not indicated for the treatment of patients with functional carcinoid tumors
  • Renal Cell Carcinoma (RCC) - Afinitor is indicated for the treatment of adult patients with advanced RCC after failure of treatment with sunitinib or sorafenib.
  • Tuberous Sclerosis Complex (TSC)-Associated Renal Angiomyolipoma - Afinitor is indicated for the treatment of adult patients with renal angiomyolipoma and TSC, not requiring immediate surgery.
  • Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA) - Afinitor and Afinitor Disperz are indicated in adult and pediatric patients aged 1 year and older with TSC for the treatment of SEGA that requires therapeutic intervention but cannot be curatively resected.
• Afinitor Disperz (everolimus tablet for oral suspension):
  • Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA) - Afinitor and Afinitor Disperz are indicated in adult and pediatric patients aged 1 year and older with TSC for the treatment of SEGA that requires therapeutic intervention but cannot be curatively resected.
  • Tuberous Sclerosis Complex (TSC)-Associated Partial-Onset Seizures - Afinitor Disperz is indicated for the adjunctive treatment of adult and pediatric patients aged 2 years and older with TSC-associated partial-onset seizures.

Coverage Criteria:

1. For diagnosis of Neuroendocrine Tumors (NET) of pancreatic origin:

• Dose does not exceed 10 mg daily, AND
• Patient is 18 years of age or older, AND
• Prescribed by or in consultation with an oncologist, AND
• Diagnosis of progressive neuroendocrine tumors of pancreatic origin, AND
• Disease is one of the following:
  • Unresectable, locally advanced
  • Metastatic, AND
• For Brand Afinitor tablets only: Trial and failure, contraindication, or intolerance to generic Afinitor tablets 

2. For diagnosis of Neuroendocrine Tumors (NET) of gastrointestinal or lung origin:

• Dose does not exceed 10 mg daily, AND
• Patient is 18 years of age or older, AND
• Prescribed by or in consultation with an oncologist, AND
• Diagnosis of progressive, well-differentiated, non-functional neuroendocrine tumors of gastrointestinal or lung origin, AND
• Disease is one of the following:
  • Unresectable, locally advanced
  • Metastatic, AND
• For Brand Afinitor tablets only: Trial and failure, contraindication, or intolerance to generic Afinitor tablets 

3. For diagnosis of Renal Cell Carcinoma (RCC):

• Dose does not exceed 10 mg daily, AND
• Patient is 18 years of age or older, AND
• Prescribed by or in consultation with an oncologist, AND
• Diagnosis of advanced/metastatic renal cell carcinoma, AND
• Trial and failure with ONE of the following:
  • Sutent (sunitinib) 
  • Nexavar (sorafenib), AND
• For Brand Afinitor tablets only: Trial and failure, contraindication, or intolerance to generic Afinitor tablets

4. For diagnosis of Tuberous Sclerosis Complex (TSC)-Associated Renal Angiomyolipoma:

• Dose does not exceed 10 mg daily, AND
• Patient is 18 years of age or older, AND
• Prescribed by or in consultation with a nephrologist, AND
• Diagnosis of renal angiomyolipoma and tuberous sclerosis complex (TSC), AND
• Patient does not require immediate surgery, AND
• For Brand Afinitor tablets only: Trial and failure, contraindication, or intolerance to generic Afinitor tablets

5. For diagnosis of Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA):

• Dose does not exceed 4.5 mg/m² orally once daily (attain blood trough concentrations according to package insert and titrate dose to attain trough concentrations of 5 ng/mL to 15 ng/mL), AND
• Patient is 1 year of age or older, AND
• Prescribed by or in consultation with an oncologist, AND
• Diagnosis of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS), AND
• Patient is not a candidate for curative surgical resection, AND
• One of the following:
  • For Brand Afinitor tablets only: Trial and failure, contraindication, or intolerance to generic Afinitor tablets, OR
  • For Brand Afinitor Disperz only: Trial and failure, contraindication, or intolerance to generic Afinitor Disperz tablet for oral suspension

6. For diagnosis of Breast Cancer:

• Dose does not exceed 4.5 mg/m² orally once daily (dose adjust based on trough concentrations), AND
• Patient is 18 years of age or older, AND
• Prescribed by or in consultation with an oncologist, AND
• Diagnosis of hormone receptor positive, HER-2 negative advanced breast cancer, AND
• Patient is post-menopausal, AND
• Trial and failure, contraindication, or intolerance to ONE of the following:
  • Femara (letrozole) 
  • Arimidex (anastrozole), AND
• Used in combination with Aromasin (exemestane), AND
• For Brand Afinitor tablets only: Trial and failure, contraindication, or intolerance to generic Afinitor tablets

7. For diagnosis of Tuberous Sclerosis Complex (TSC)-Associated Partial-Onset Seizures:

• Dose does not exceed 5 mg/m² orally once daily (dose adjust based on trough concentrations), AND
• Patient is 2 years of age or older, AND
• Prescribed by or in consultation with a neurologist, AND
• Diagnosis of TSC-associated partial-onset seizures, AND
• Used as adjunctive therapy, AND
• For Brand Afinitor Disperz only: Trial and failure, contraindication, or intolerance to generic Afinitor Disperz tablet for oral suspension

Reauthorization Criteria:

For diagnosis of NET, RCC, renal angiomyolipoma with TSC, SEGA with TSC, breast cancer:

• Dose does not exceed Food and Drug administration (FDA) approved maximum dosing as listed above, AND
• Patient does not show evidence of progressive disease while on therapy

For diagnosis of partial-onset seizures with TSC:

• Dose does not exceed Food and Drug administration (FDA) approved maximum dosing as listed above, AND
• Patient shows reduction in seizure frequency while on therapy 

Coverage Duration: 

• Initial: 
  • All above indications: 1 year
• Reauthorization: 
  • All above indications: 1 year

Authorization is not covered for the following:

The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information: 

• Therapeutic Drug Monitoring (TDM) and Dose Titration for Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA) and TSC-Associated Partial-Onset Seizures:
  • Monitor everolimus whole blood trough concentrations at time points recommended by the manufacturer’s package insert.
  • Titrate the dose to attain trough concentrations of 5 ng/mL to 15 ng/mL.
  • Adjust the dose using the following equation:
    • New dose* = current dose x (target concentration divided by current concentration)
    • *The maximum dose increment at any titration must not exceed 5 mg. Multiple dose titrations may be required to attain the target trough concentration.
• Afinitor and Afinitor Disperz are two different dosage forms. Select the recommended dosage form based on the indication. Do not combine Afinitor and Afinitor Disperz to achieve the total dose.
• Modify the dosage for patients with hepatic impairment or for patients taking drugs that inhibit or induce P-glycoprotein (P-gp) and CYP3A4.
• Afinitor/Afinitor Disperz is contraindicated in patients with clinically significant hypersensitivity to everolimus or to other rapamycin derivatives
• Warnings/precautions include:
  • Non-infectious Pneumonitis
  • Infections
  • Severe Hypersensitivity Reactions
  • Angioedema with Concomitant Use of Angiotensin-Converting Enzyme (ACE) Inhibitors
  • Stomatitis
  • Renal Failure
  • Risk of Impaired Wound Healing
  • Geriatric Patients
  • Metabolic Disorders
  • Myelosuppression
  • Risk of Infection or Reduced Immune Response with Vaccination
  • Radiation Sensitization and Radiation Recall
  • Embryo-Fetal Toxicity
• The safety and effectiveness of Afinitor/Afinitor Disperz in pediatric patients have not been established in:
  • Hormone receptor-positive, HER2-negative breast cancer
  • Neuroendocrine tumors (NET)
  • Renal cell carcinoma (RCC)
  • TSC-associated renal angiomyolipoma
     

Policy Updates:

• 2/21/2023 – New policy approved by P&T.

References:

1.    Afinitor and Afinitor Disperz Prescribing Information. Novartis Pharmaceuticals Corporation. East Hanover, NJ. February 2022