Everolimus

(Afinitor®)

Afinitor®

Drug updated on 11/1/2024

Dosage FormTablet (oral; afinitor: 2.5 mg, 5 mg, 7.5 mg, and 10 mg); Tablet (oral suspension; afinitor disperz: 2 mg, 3 mg, and 5 mg)
Drug ClassKinase Inhibitors
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • 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
  • Afinitor is indicated for the treatment of adults 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
  • Afinitor is indicated for the treatment of adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib
  • Afinitor is indicated for the treatment of adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery
  • Afinitor and Afinitor Disperz are indicated for the treatment of adult and pediatric patients aged 1 year and older with TSC who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected
  • Afinitor Disperz is indicated for the adjunctive treatment of adult and pediatric patients aged 2 years and older with TSC associated partial-onset seizures.

Latest News

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Summary
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  • This summary is based on the review of 19 systematic review(s)/meta-analysis(es). [1-19]
  • Renal Cell Carcinoma (RCC): Lenvatinib combined with Everolimus ranked highest in effectiveness, showing superior overall survival (OS) (HR (hazard ratio) = 0.44; 95% CI (confidence interval) = 0.24-0.82), progression-free survival (PFS) (HR = 0.13; 95% CI = 0.07-0.24), and objective response rate (ORR) (OR (odds ratio) = 35.95; 95% CI = 11.55-111.87) compared to placebo. Cabozantinib ranked second in OS (HR = 0.57) and PFS (HR = 0.19), while Nivolumab had the lowest risk of severe adverse events (SAE).
  • Tuberous Sclerosis Complex (TSC): Oral Everolimus demonstrated significant effectiveness in reducing renal angiomyolipoma size by 50% (RR = 24.69; P = 0.001), reducing SEGA tumor size by 50% (RR = 27.85; P = 0.02), and decreasing seizure frequency by 25% and 50% (P = 0.0001 and P = 0.0004, respectively). It also showed notable improvement in skin responses (RR = 5.78; P = 0.0002).
  • Neuroendocrine Tumors (NETs): Everolimus and Sirolimus effectively stabilized lung function and reduced angiomyolipomas in patients with LAM, with Everolimus also enhancing progression-free survival (PFS) and OS in patients with metastatic NETs, highlighting its clinical benefit in these conditions.
  • Renal Cell Carcinoma (RCC): The combination of Everolimus with Lenvatinib was associated with a higher risk of severe adverse events (SAEs) compared to other treatments, necessitating frequent dose adjustments, interruptions, or withdrawals due to adverse effects. Nivolumab presented the lowest incidence of SAEs among the RCC treatments.
  • Tuberous Sclerosis Complex (TSC): While overall adverse events were similar between Everolimus and placebo, patients on Everolimus experienced more severe adverse events, leading to increased treatment modifications.
  • Neuroendocrine Tumors (NETs): Everolimus and Sirolimus were generally well-tolerated with primarily mild side effects, although Everolimus showed a higher rate of severe adverse events compared to placebo.
  • Population studies included previously treated adolescents and adults with metastatic renal cell carcinoma (RCC), neuroendocrine tumors (NETs), and tuberous sclerosis complex (TSC), with age ranges spanning from 3 months to 65 years for TSC. Subgroup analyses identified no significant differences in adverse events between children and adults with TSC and showed that RCC patients with higher mTOR inhibitor levels had increased discontinuation rates due to adverse effects.

Product Monograph / Prescribing Information

Document TitleYearSource
Afinitor (everolimus) Prescribing Information.2022Novartis Pharmaceuticals Corporation, East Hanover, NJ

Systematic Reviews / Meta-Analyses

Document TitleYearSource
Coronary stent implantation links to the occurrence of eosinophilia and interstitial pneumonia: a case report and systematic review2024Bmc Pulmonary Medicine
Network meta-analysis of second line and beyond treatment options in metastatic clear cell renal cell carcinoma2024Urologic Oncology
Rapamycin and rapalogs for tuberous sclerosis complex2023The Cochrane Database of Systematic Reviews
Everolimus and temsirolimus are not the same second-line in metastatic renal cell carcinoma: a systematic review and meta-analysis2023Cost Effectiveness and Resource Allocation : C/e
Mammalian Target of Rapamycin Inhibitors and Kidney Function After Thoracic Transplantation: A Systematic Review and Recommendations for Management of Lung Transplant Recipients2023Transplantation
Optimizing targeted drug selection in combination therapy for patients with advanced or metastatic renal cell carcinoma: A systematic review and network meta-analysis of safety2023Cancer Medicine
Systemic therapies for metastatic renal cell carcinoma in the second-line setting: A systematic review and network meta-analysis2022Medicine
Health-Related Quality of Life (HRQoL) in Neuroendocrine Tumors: A Systematic Review2022Cancers
Treatment for gastrointestinal and pancreatic neuroendocrine tumours: a network meta-analysis2021The Cochrane Database of Systematic Reviews
Suicidality Risk of Newer Antiseizure Medications: A Meta-analysis2021Jama Neurology
Comparative efficacy of treatments for previously treated patients with advanced esophageal and esophagogastric junction cancer: A network meta-analysis2021Plos One
Treatment of Cardiac Rhabdomyomas with mTOR Inhibitors in Children with Tuberous Sclerosis Complex-A Systematic Review2021International Journal of Environmental Research and Public Health
Relationship between metabolic toxicity and efficacy of everolimus in patients with neuroendocrine tumors: A pooled analysis from the randomized, phase 3 RADIANT-3 and RADIANT-4 trials2021Cancer
Efficacy of second-line treatments for patients with advanced human epidermal growth factor receptor 2 positive breast cancer after trastuzumab-based treatment: a systematic review and bayesian network analysis2021Journal of Cancer
Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials2021Cancers
A network meta-analysis of efficacy and safety of first-line and second-line therapies for the management of metastatic renal cell carcinoma2021Journal of Clinical Pharmacy and Therapeutics
Endocrine therapies in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, pretreated, advanced breast cancer: A network meta-analysis2020Medicine
The efficacy and safety of pharmacological treatments for lymphangioleiomyomatosis2020Respiratory Research
Meta-Analysis of Randomized Clinical Trials Comparing Active Treatment with Placebo in Metastatic Neuroendocrine Tumors2019The Oncologist

Clinical Practice Guidelines