Difference between revisions of "Everolimus (Afinitor)"

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==History of changes in FDA indication==
 
==History of changes in FDA indication==
 
===[[Breast cancer, ER-positive|HR+ Breast cancer]]===
 
===[[Breast cancer, ER-positive|HR+ Breast cancer]]===
−
*7/20/2012: Approval expanded to include postmenopausal women with advanced [[Biomarkers#HR|hormone receptor]]-[[Biomarkers#Expression|positive]], [[Biomarkers#HER2|HER2]]-[[Biomarkers#Normal_expression|negative]] [[breast cancer]] (advanced HR+ BC) [[Breast_cancer#Exemestane_.26_Everolimus|in combination with exemestane]] after failure of treatment with [[Breast_cancer#Letrozole_monotherapy_2 | letrozole]] or [[Breast_cancer#Anastrozole_monotherapy_2 | anastrozole]]. ''(Based on BOLERO-2)''
+
*2012-07-20: Approval expanded to include postmenopausal women with advanced [[Biomarkers#HR|hormone receptor]]-[[Biomarkers#Expression|positive]], [[Biomarkers#HER2|HER2]]-[[Biomarkers#Normal_expression|negative]] [[breast cancer]] (advanced HR+ BC) [[Breast_cancer#Exemestane_.26_Everolimus|in combination with exemestane]] after failure of treatment with [[Breast_cancer#Letrozole_monotherapy_2 | letrozole]] or [[Breast_cancer#Anastrozole_monotherapy_2 | anastrozole]]. ''(Based on BOLERO-2)''
 
===[[Neuroendocrine tumor]]===
 
===[[Neuroendocrine tumor]]===
−
*2/26/2016: Approval expanded for the treatment of adult patients with progressive, well-differentiated non-functional, [[Neuroendocrine tumor |neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin]] with unresectable, locally advanced or metastatic disease. ''(Based on RADIANT-4)''
+
*2016-02-26: Approval expanded for the treatment of adult patients with progressive, well-differentiated non-functional, [[Neuroendocrine tumor |neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin]] with unresectable, locally advanced or metastatic disease. ''(Based on RADIANT-4)''
 
===[[Pancreatic NET]]===
 
===[[Pancreatic NET]]===
−
*5/5/2011: Approval expanded to include progressive [[Pancreatic NET | neuroendocrine tumors of pancreatic origin (PNET)]] that is unresectable, locally advanced or metastatic. ''(Based on RADIANT-3)''
+
*2011-05-05: Approval expanded to include progressive [[Pancreatic NET | neuroendocrine tumors of pancreatic origin (PNET)]] that is unresectable, locally advanced or metastatic. ''(Based on RADIANT-3)''
 
===[[Renal cell carcinoma]]===
 
===[[Renal cell carcinoma]]===
−
*3/30/2009: '''Initial approval''' for the treatment of patients with advanced [[Renal cell carcinoma | renal cell carcinoma]] after failure of treatment with [[Renal_cell_carcinoma#Sunitinib_monotherapy | sunitinib]] or [[Renal_cell_carcinoma#Sorafenib_monotherapy | sorafenib]]. ''(Based on RECORD-1)''
+
*2009-03-30: '''Initial approval''' for the treatment of patients with advanced [[Renal cell carcinoma | renal cell carcinoma]] after failure of treatment with [[Renal_cell_carcinoma#Sunitinib_monotherapy | sunitinib]] or [[Renal_cell_carcinoma#Sorafenib_monotherapy | sorafenib]]. ''(Based on RECORD-1)''
 
===Tuberous sclerosis complex-associated renal angiomyolipoma===
 
===Tuberous sclerosis complex-associated renal angiomyolipoma===
−
*4/26/2012: Accelerated approval for adults with [[renal angiomyolipoma]] and tuberous sclerosis complex (TSC), not requiring immediate surgery. ''(Based on EXIST-2)''
+
*2012-04-26: Accelerated approval for adults with [[renal angiomyolipoma]] and tuberous sclerosis complex (TSC), not requiring immediate surgery. ''(Based on EXIST-2)''
−
**2/18/2016: Converted to regular approval
+
**2016-02-18: Converted to regular approval
 
===Tuberous sclerosis complex-associated [[subependymal giant cell astrocytoma]]===
 
===Tuberous sclerosis complex-associated [[subependymal giant cell astrocytoma]]===
−
*10/29/2010: Accelerated approval for [[Subependymal giant cell astrocytoma | subependymal giant cell astrocytoma (SEGA)]] associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. ''(Based on CCHMC 06-07-50)''
+
*2010-10-29: Accelerated approval for [[Subependymal giant cell astrocytoma | subependymal giant cell astrocytoma (SEGA)]] associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. ''(Based on CCHMC 06-07-50)''
−
**1/29/2016: Converted to regular approval for [[Subependymal giant cell astrocytoma | subependymal giant cell astrocytoma (SEGA)]] associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. ''(Based on EXIST-1)''
+
**2016-01-29: Converted to regular approval for [[Subependymal giant cell astrocytoma | subependymal giant cell astrocytoma (SEGA)]] associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. ''(Based on EXIST-1)''
  
 
==History of changes in EMA indication==
 
==History of changes in EMA indication==
−
*8/2/2009: Initial marketing authorization as Afinitor.
+
*2009-08-02: Initial marketing authorization as Afinitor.
 +
 
 +
==History of changes in Health Canada indication==
 +
*2011-06-30: Initial notice of compliance with conditions
 +
*2016-09-23: Conditions were met
  
 
==Also known as==
 
==Also known as==
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[[Category:Oral medications]]
 
[[Category:Oral medications]]
 
[[Category:Protein expression-specific medications]]
 
[[Category:Protein expression-specific medications]]
−
 
  
 
[[Category:mTOR inhibitors]]
 
[[Category:mTOR inhibitors]]
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[[Category:EMA approved in 2009]]
 
[[Category:EMA approved in 2009]]
 
[[Category:FDA approved in 2009]]
 
[[Category:FDA approved in 2009]]
 +
[[Category:Health Canada approved in 2011]]
 
[[Category:PMDA approved drugs]]
 
[[Category:PMDA approved drugs]]
  
 
[[Category:WHO Essential Cancer Medicine]]
 
[[Category:WHO Essential Cancer Medicine]]

Revision as of 12:54, 29 March 2023

General information

Class/mechanism: mTOR kinase inhibitor; mTOR (mammalian target of rapamycin) is a serine-threonine kinase downstream of the PI3K/AKT pathway. In vitro, everolimus has been found to reduce cell proliferation, angiogenesis, and glucose uptake. Everolimus forms inhibitory complexes with mTORC1 by binding to the intracellular protein FKBP-12. Reduces activity of downstream effectors of mTOR that are involved in protein synthesis, S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E binding protein (4E-BP1). Reduces expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1).[1][2][3]
Route: PO
Extravasation: n/a

  • Anecdotally, taking the pill in a small amount of whipped/sour cream[4] or putting the pill in a marshmallow[5] may decrease the likelihood of developing stomatitis/mucositis.

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]

Diseases for which it is established (work in progress)

Diseases for which it is used

Patient drug information

History of changes in FDA indication

HR+ Breast cancer

Neuroendocrine tumor

Pancreatic NET

Renal cell carcinoma

Tuberous sclerosis complex-associated renal angiomyolipoma

  • 2012-04-26: Accelerated approval for adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. (Based on EXIST-2)
    • 2016-02-18: Converted to regular approval

Tuberous sclerosis complex-associated subependymal giant cell astrocytoma

  • 2010-10-29: Accelerated approval for subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. (Based on CCHMC 06-07-50)
    • 2016-01-29: Converted to regular approval for subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapeutic intervention but are not candidates for curative surgical resection. (Based on EXIST-1)

History of changes in EMA indication

  • 2009-08-02: Initial marketing authorization as Afinitor.

History of changes in Health Canada indication

  • 2011-06-30: Initial notice of compliance with conditions
  • 2016-09-23: Conditions were met

Also known as

  • Code names: RAD001, RAD-001
  • Brand names: Advacan, Afinitor, Afinitor Disperz, Certican, Everecan, EverGraf, Evermil, Evertor, Rapact, Rolimus, Votubia, Zortress

References

  1. ↑ 1.0 1.1 1.2 Everolimus (Afinitor) package insert
  2. ↑ Everolimus (Afinitor) package insert (locally hosted backup)
  3. ↑ Afinitor manufacturer's website
  4. ↑ Discussion between Sara Hurvitz, MD and Neil Love, MD, 2012
  5. ↑ Simeon Bennett, Novartis’ Afinitor gets OK of FDA, Bloomberg News (July 29, 2012). Retrieved 9/11/2012.
  6. ↑ Everolimus (Afinitor) patient drug information (Chemocare)
  7. ↑ Everolimus (Afinitor) patient drug information (UpToDate)
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