# Everolimus

Source: https://onco.cc/drugs/everolimus/  
OnCo record `everolimus` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An mTOR-blocking pill that doubled progression-free time with exemestane in 2012 and is now paired with the oral SERD giredestrant.

## Summary

Everolimus is a rapalog that binds FKBP12 and allosterically inhibits mTORC1, a growth-signalling hub downstream of PI3K and AKT. It is approved in HR-positive breast cancer with exemestane after non-steroidal aromatase inhibitor failure, in progressive pancreatic, lung and GI neuroendocrine tumours, and in advanced RCC after sunitinib or sorafenib. BOLERO-2 showed PFS of 7.8 versus 3.2 months for everolimus plus exemestane versus exemestane alone, with no OS benefit; RADIANT-3 and RADIANT-4 showed PFS of 11.0 versus 4.6 and 3.9 months in NETs. Stomatitis (mitigated by dexamethasone mouthwash, SWISH), pneumonitis and hyperglycaemia are the main toxicities. evERA (2025) revived it as the partner of giredestrant after CDK4/6 inhibitors; it is the comparator beaten in LITESPARK-005 and COMPETE. For a newcomer, it is a growth-pathway pill with several niches rather than one dominant use.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Brand: Afinitor
- Modality: Small-molecule mTOR inhibitor
- Mechanism: Allosteric mTORC1 inhibitor (rapalog) via FKBP12.
- Approvals: US 2012: HR+/HER2- advanced breast cancer with exemestane after NSAI failure; US 2011: Progressive pancreatic NETs; US 2016: Progressive non-functional lung and GI NETs; US 2009: Advanced RCC after sunitinib or sorafenib
- Dosing: Oral; 10 mg once daily
- Toxicity (grade 3+): Stomatitis 8%; Pneumonitis 3%; Hyperglycaemia 5%

## Notes

- In neuroendocrine tumours: RADIANT-3 (2011) gave PFS 11.0 versus 4.6 months in pancreatic NETs and RADIANT-4 (2016) PFS 11.0 versus 3.9 months in lung and GI NETs; it is now the comparator that 177Lu-edotreotide beat in COMPETE. In RADIANT-3 stomatitis affected 64 percent (7 percent grade 3 or higher), rash 49 percent and pneumonitis 17 percent; dexamethasone mouthwash (SWISH) prevents most stomatitis.
- In kidney cancer: RECORD-1 (2008) gave PFS 4.9 versus 1.9 months against placebo after a VEGF-TKI, making everolimus the second-line standard from 2009; it has since been beaten by nivolumab (CheckMate 025), cabozantinib (METEOR), lenvatinib plus everolimus (Study 205) and belzutifan (LITESPARK-005), and is now mostly a comparator arm and a partner for lenvatinib at 5 mg daily. Feedback activation of AKT limits its cytostatic effect.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Everolimus
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Everolimus

## Connected records

- cancers: [Advanced cutaneous squamous cell carcinoma](https://onco.cc/cancers/advanced-cutaneous-scc/), [Chromophobe renal cell carcinoma](https://onco.cc/cancers/chromophobe-rcc/), [Clear cell renal cell carcinoma](https://onco.cc/cancers/clear-cell-rcc/), [Eosinophilic solid and cystic renal cell carcinoma](https://onco.cc/cancers/eosinophilic-solid-cystic-renal-cell-carcinoma/), [Epithelioid haemangioendothelioma](https://onco.cc/cancers/epithelioid-haemangioendothelioma/), [Glucagonoma](https://onco.cc/cancers/glucagonoma/), [Grade 3 well-differentiated neuroendocrine tumour](https://onco.cc/cancers/grade-3-net/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [HR-positive metastatic breast cancer after CDK4/6 inhibitors](https://onco.cc/cancers/hr-positive-metastatic-post-cdk46/), [Kaposi sarcoma](https://onco.cc/cancers/kaposi-sarcoma/), [Lung neuroendocrine tumours (typical and atypical carcinoid)](https://onco.cc/cancers/lung-net/), [Meningioma](https://onco.cc/cancers/meningioma/), [Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)](https://onco.cc/cancers/multiple-endocrine-neoplasia/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Pancreatic neuroendocrine tumours](https://onco.cc/cancers/pancreatic-net/), [Perivascular epithelioid cell tumour (PEComa)](https://onco.cc/cancers/pecoma/), [Rare cancers of childhood (NCI PDQ umbrella)](https://onco.cc/cancers/rare-childhood-cancers/), [Relapsed and refractory classical Hodgkin lymphoma](https://onco.cc/cancers/relapsed-refractory-hodgkin-lymphoma/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Small intestinal neuroendocrine tumours](https://onco.cc/cancers/small-intestinal-net/), [Somatostatinoma](https://onco.cc/cancers/somatostatinoma/), [Thymic carcinoma](https://onco.cc/cancers/thymic-carcinoma/), [Thymoma (WHO types A, AB, B1, B2 and B3)](https://onco.cc/cancers/thymoma/), [Thymoma and thymic carcinoma](https://onco.cc/cancers/thymic-epithelial/), [VIPoma](https://onco.cc/cancers/vipoma/)
- technologies: [PI3K, AKT and mTOR inhibitors](https://onco.cc/technologies/pi3k-akt-mtor-inhibitors/), [Rapamycin and mTOR inhibition for ageing](https://onco.cc/technologies/rejuv-frontier-rapamycin-ageing/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [AKT](https://onco.cc/targets/akt/), [FKBP12 (FKBP1A)](https://onco.cc/targets/fkbp12/), [mTOR](https://onco.cc/targets/mtor/), [PIK3CA / PI3K-alpha](https://onco.cc/targets/pik3ca/)
- companies: [Novartis](https://onco.cc/companies/novartis/)
- pathways: [Choline metabolism in cancer](https://onco.cc/pathways/choline-metabolism-in-cancer/), [Endometrial cancer (KEGG map)](https://onco.cc/pathways/endometrial-cancer-signalling/), [mRNA translation (eIF4F / mTOR)](https://onco.cc/pathways/mrna-translation-eif4f/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [Renal cell carcinoma (KEGG map)](https://onco.cc/pathways/renal-cell-carcinoma-signalling/)
- terms: [Hyperglycaemia (PI3K/AKT inhibitor class effect)](https://onco.cc/terms/hyperglycaemia/), [PTEN loss](https://onco.cc/terms/pten-loss/)
- trials: [A Phase Ib/II Study to Evaluate Multiple Combination Therapies of FWD1802 in Patients With ER+/HER2- BC](https://onco.cc/trials/nct07002177/), [A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer](https://onco.cc/trials/nct04802759/), [BOLERO-2](https://onco.cc/trials/bolero-2/), [CheckMate 025](https://onco.cc/trials/checkmate-025/), [CLEAR (KEYNOTE-581)](https://onco.cc/trials/clear/), [COMPETE](https://onco.cc/trials/compete/), [Efficacy and Safety of Radiotherapy Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus.](https://onco.cc/trials/nct05918302/), [evERA](https://onco.cc/trials/evera/), [Everolimus Combined With PD-1 in Advanced Colorectal Cancer Patients](https://onco.cc/trials/nct06301386/), [Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies](https://onco.cc/trials/nct07340541/), [FUSCC Refractory TNBC Platform Study (FUTURE2.0)](https://onco.cc/trials/nct05749588/), [LITESPARK-005](https://onco.cc/trials/litespark-005/), [Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE](https://onco.cc/trials/nct04919226/), [Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Participants With Metastatic Breast Cancer](https://onco.cc/trials/nct05563220/), [Phase 1/2 Study to Evaluate EP0062 as Monotherapy and in Combination in Patients With Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer](https://onco.cc/trials/nct05573126/), [RADIANT-3 and RADIANT-4](https://onco.cc/trials/radiant-3-4/), [Sirolimus for Injection (Albumin Bound) Combined With Octreotide Long-acting Injection in Patients With Metastatic Gastroenteropancreatic Neuroendocrine Tumors](https://onco.cc/trials/nct07165886/), [Study of Belzutifan (MK-6482) Plus Fulvestrant for ER+/HER2- Metastatic Breast Cancer (MK-6482-029/LITESPARK-029)](https://onco.cc/trials/nct06428396/), [Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer](https://onco.cc/trials/nct05725200/)
- ideas: [Block the recycling that keeps dormant cells alive](https://onco.cc/ideas/idea-bio2-autophagy-block-mrd/)
- key papers: [ASPEN: everolimus versus sunitinib in metastatic non-clear cell renal cell carcinoma](https://onco.cc/key-papers/paper-aspen-armstrong-lancet-oncol-2016/), [RADIANT-3: everolimus for advanced pancreatic neuroendocrine tumours](https://onco.cc/key-papers/paper-radiant-3-everolimus-pnet-yao-nejm-2011/), [RADIANT-4: everolimus for advanced non-functional neuroendocrine tumours of the lung or gastrointestinal tract](https://onco.cc/key-papers/paper-radiant-4-everolimus-lancet-2016/), [Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-esmo-thymic-epithelial-tumours-guideline-ann-oncol-2015/)
- drugs: [Diazoxide](https://onco.cc/drugs/diazoxide/), [Pasireotide](https://onco.cc/drugs/pasireotide/), [Sirolimus protein-bound particles](https://onco.cc/drugs/sirolimus-albumin-bound/)
- roadmaps: [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/)

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JSON: https://onco.cc/api/v1/entities/everolimus.json