Everolimus
An mTOR-blocking pill that doubled progression-free time with exemestane in 2012 and is now paired with the oral SERD giredestrant.
Overview
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.
1.Everolimus slips into a pocket on its target.
- Route
- Oral
- Schedule
- 10 mg once daily
- Dose modifications
- 5 mg for stomatitis or pneumonitis
- Monitoring
- Glucose, lipids, pneumonitis symptoms; steroid mouthwash prophylaxis
- Medicare
- Part D (self-administered)
Oral, self-administered, so it is a Part D drug: covered through a stand-alone Part D plan or Medicare Advantage drug benefit, usually on the specialty tier with 25 to 33% coinsurance until the annual cap ($2,000 in 2025, $2,100 in 2026). Generic everolimus is available and inexpensive relative to Afinitor.
- Commercial insurance
- covered on label
Multi-source generic on low-cost tiers; usually no prior authorisation. Cash prices without insurance are modest. Plans require the generic.
Sources: Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.
- Appraised for
- Advanced renal cell carcinoma after previous treatment
- Notes
- Also HR-positive breast cancer with exemestane (TA421, 2016) and neuroendocrine tumours (TA449, 2017, with sunitinib).
- NHS England
- Routinely funded for the appraised indication (or via managed access)
Sources: NICE TA432 · SMC advice: everolimus. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
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Approvals
| Region | Year | Indication |
|---|---|---|
| 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 |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Stomatitis | 59% | 8% |
| Pneumonitis | 16% | 3% |
| Hyperglycaemia | 14% | 5% |
Events listed without rates were not read from a primary source; see the label. Blank cells mean the figure was not sourced, not that it is zero.
Trials
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Landmark trials
Notes
top- 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.
Latest papers
topQuery for this drug: (TITLE:"Everolimus" OR ABSTRACT:"Everolimus" OR TITLE:"Afinitor" OR ABSTRACT:"Afinitor") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Everolimus, not a curated reading list.
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