Afinitor

Advanced hormone receptor-positive/HER2-negative breast cancer (with exemestane, after letrozole or anastrozole failure); Advanced renal cell carcinoma after failure of sunitinib or sorafenib; Progressive neuroendocrine tumors of pancreatic origin (PNET); Progressive, well-differentiated, non-functional neuroendocrine tumors of GI or lung origin; Renal angiomyolipoma with TSC; Subependymal giant cell astrocytoma (SEGA) with TSC

Breast cancer/RCC/PNET/GI-NET: 10 mg orally once daily
SEGA: Dose based on BSA, titrate to trough levels of 5-15 ng/mL
Take consistently with or without food

Tablets: 2.5 mg, 5 mg, 7.5 mg, 10 mg; Tablets for oral suspension (Afinitor Disperz): 2 mg, 3 mg, 5 mg

Refer to the complete prescribing information for contraindications. Afinitor prescribing should account for patient-specific factors including hypersensitivity to the active ingredient or any excipients.

• Non-Infectious Pneumonitis: Reported in up to 19% of patients. Monitor with imaging and clinical assessment.
• Infections: Increased risk of bacterial, fungal, viral, and protozoal infections including reactivation of hepatitis B.
• Stomatitis: Up to 67% incidence. Manage with alcohol-free mouthwash.
• Metabolic: Hyperglycemia (57%), hyperlipidemia, monitor fasting glucose and lipids.

Stomatitis (67%), infections (50%), rash (39%), fatigue (38%), diarrhea (34%), decreased appetite (31%), nausea (29%), edema (25%), hyperglycemia (57%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine/threonine kinase downstream of the PI3K/AKT pathway. Everolimus binds to FKBP-12, and this complex inhibits mTOR complex 1 (mTORC1), reducing protein synthesis, cell proliferation, and angiogenesis in tumor cells.

Tmax: 1-2 hours. Half-life: approximately 30 hours. Protein binding: ~74%. Metabolized by CYP3A4 and P-gp. Steady-state reached in 2 weeks. Blood-to-plasma ratio: 17-73%. Excreted in feces (80%) and urine (5%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• RECORD-1 — Everolimus vs. placebo in advanced RCC after VEGFR-TKI failure. Phase III, n=416.
  🔬 NCT00410124 ↗ 📄 Primary Publication ↗
• BOLERO-2 — Everolimus + exemestane vs. placebo + exemestane in HR+/HER2- advanced breast cancer. Phase III, n=724.
  🔬 NCT00863655 ↗ 📄 Primary Publication ↗

Afinitor has FDA-approved indications across the following cancer types covered on PipelineEvidence: