Everolimus
Rapamycin analog (RAD001); used in oncology and tested for immune function in older adults.
A rapamycin derivative used in clinic.
RAD001. Same FKBP12-dependent allosteric mechanism as rapamycin, better oral pharmacokinetics; the clinical evidence base here is trial evidence, not mechanism.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| S | Synthesis of human data | 1 |
| H | Human study | 11 |
| A | Animal model | 1 |
| RT | Registered trial, no results yet | 1 |
Studies
| Year | Evidence | Study |
|---|---|---|
| 2024 | S | Targeting ageing with rapamycin and its derivatives in humans: a systematic review LEE2024 The first systematic review of rapamycin/rapalogs in humans for aging. Screened 18,400 articles, included 19 studies. Found improvements in immune, cardiovascular, and skin (integumentary) parameters; NO significant effect on endocrine, muscular, or neurological systems. No serious adverse events in healthy people, but more infections and raised cholesterol/triglycerides in people with age-related disease. This is the highest-tier human-evidence summary in the whole Atlas - it aggregates many individual human studies rather than reporting one. |
| 2026 | H | EVERolimus effectiveness after proGREssion on ENdocrine therapy plus CDK4/6 inhibitor for ER-positive/HER2-negative advanced breast cancer: EVERGREEN study MAR2026 Everolimus added to endocrine therapy provided modest but statistically significant PFS benefit (5.0 vs 4.3 months; HR 0.68) in ER+/HER2- advanced breast cancer post-CDK4/6 inhibitor progression, without demonstrable OS benefit, supporting selective use. Retrospective and non-randomised, so treatment-selection bias cannot be excluded. |
| 2026 | H | Everolimus for the treatment of neuropsychological deficits in tuberous sclerosis complex: findings from the TRON multicentre randomised controlled trial SAX2026 In a multicentre RCT of TSC patients (n=38 randomised, 2:1 everolimus:placebo), 24 weeks of everolimus produced similarly large 'responder' rates for neuropsychological improvement as placebo (87% vs 75%), suggesting large practice/placebo effects rather than a clear drug benefit on cognition -- despite everolimus's established efficacy for TSC tumours and epilepsy. Adverse events were more frequent with everolimus (88% vs 61.5%). |
| 2026 | H | Tumor fat composition predicts response to everolimus and supports low-dose therapy in TSC-associated renal angiomyolipomas: a multicenter prospective study GAO2026B In a multicenter prospective cohort of 183 TSC-associated renal angiomyolipoma patients, everolimus reduced tumor volume by >=50% in 44% of patients at 3 months and 83% at 6 months; fat-poor lesions responded significantly better than fat-rich ones. A low-dose everolimus regimen showed comparable efficacy to standard dose with fewer adverse events (notably less oral mucositis), though tumor regrowth occurred after treatment discontinuation. |
| 2018 | H | TORC1 inhibition enhances immune function and reduces infections in the elderly MAN2018 The strongest human evidence that mTOR inhibition can rejuvenate a specific function of aging - immunity. In 264 elderly people, a low-dose combination that selectively hits TORC1 significantly reduced infections over the following year and boosted antiviral gene expression and flu-vaccine response. The follow-up to Mannick 2014. |
| 2014 | H | mTOR inhibition improves immune function in the elderly MAN2014 Low-dose everolimus improved influenza vaccine response by ~20% and reduced PD-1 expression on T lymphocytes. |
| 2013 | H | Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial FRA2013 Phase 3 RCT (n=117) in tuberous sclerosis, the disease where mTOR is stuck ON by a genetic fault. Everolimus shrank brain tumors (SEGA) by >=50% in 35% of patients versus 0% on placebo. Because the underlying cause here is direct mTOR overactivation, this is arguably the cleanest randomised human evidence that blocking mTOR works in a genetically defined mTORopathy -- which does not extend to mTOR inhibition in people without such a mutation. |
| 2013 | H | Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial BIS2013 The companion phase 3 RCT (n=118) to EXIST-1, targeting kidney tumors (angiomyolipomas) in tuberous sclerosis and LAM. Everolimus shrank them by >=50% in 42% of patients versus 0% on placebo. Together EXIST-1 and -2 sealed everolimus as a disease-modifying therapy across multiple TSC tumor types. |
| 2012 | H | Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer (BOLERO-2) BAS2012 A phase 3 RCT (n=724) proving mTOR matters in a common cancer. When hormone-therapy stops working in breast cancer, it's partly because mTOR switches on. Adding everolimus more than doubled progression-free survival (10.6 vs 4.1 months by central review) - leading to FDA approval. Main toxicity was stomatitis. |
| 2011 | H | Everolimus for advanced pancreatic neuroendocrine tumors (RADIANT-3) YAO2011 A phase 3 RCT (n=410) that made everolimus a standard treatment for pancreatic neuroendocrine tumors. It more than doubled progression-free survival (11.0 vs 4.6 months, a 65% reduction in risk of progression/death) with mostly mild side effects. Another FDA-approved indication built on blocking mTOR. |
| 2010 | H | Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis KRU2010 In patients whose TSC1/TSC2 mutations cause brain tumors, everolimus shrank tumor volume by 30%+ in three-quarters of patients. Open-label and uncontrolled (n=28); randomised confirmation came later (FRA2013). |
| 2008 | H | Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial MOT2008 Everolimus extended median progression-free survival from 1.9 to 4.0 months versus placebo in metastatic renal cell carcinoma. |
| 2026 | A | mTOR inhibition augments antitumor immune effector response by reprogramming the TP53-mutant, immune-cold HNSCC tumor microenvironment NAT2026 In syngeneic TP53-mutant HNSCC mouse models, the mTOR inhibitor everolimus reprogrammed the immune-cold tumor microenvironment: it increased CD8+ T cell and dendritic cell infiltration, reduced Tregs and HIF-1α/VEGFA-driven MDSC recruitment, boosted TNF-α/CXCL10 chemokine signaling, and reduced PD-1/PD-L1 expression — restoring T-cell cytotoxic competence and suppressing tumor growth. |
| RT | Everolimus Aging Study (EVERLAST): Clinical Evaluation of mTORC1 Inhibition for Geroprotection NCT05835999 Currently active phase 2 trial (NCT05835999) directly testing this Atlas's open dosing hypothesis: whether daily low-dose (0.5mg) versus weekly (5mg) everolimus can improve aging biomarkers and insulin resistance in humans without the metabolic penalty seen with continuous higher-dose rapalog use. No results yet - status ACTIVE_NOT_RECRUITING. |