How Everolimus Is Used to Treat Glioblastoma: Current Evidence and Clinical Insights

When a glioblastoma diagnosis comes, the road ahead feels overwhelming. Standard treatments-surgery, radiation, temozolomide-often slow the tumor but rarely stop it for long. That’s where everolimus comes in. It’s not a cure, but for some patients, it’s a meaningful option when other drugs have run out of steam.

What Everolimus Is and How It Works

Everolimus is a drug that blocks a protein called mTOR. This protein acts like a switch inside cells, telling them when to grow and divide. In glioblastoma, that switch gets stuck in the "on" position. Cancer cells multiply nonstop, ignoring the body’s normal stop signals.

Everolimus doesn’t kill cancer cells directly. Instead, it shuts down the mTOR pathway. Without it, tumor cells struggle to make the proteins and energy they need to survive. Think of it like cutting the fuel line to a car engine-it doesn’t explode the car, but the engine eventually stalls.

Everolimus is FDA-approved for other cancers, like kidney and breast cancer. Its use in glioblastoma is off-label, meaning it’s not officially approved for brain tumors-but doctors use it based on strong clinical data. It’s an oral pill, taken daily, and it crosses the blood-brain barrier better than many other targeted therapies, which is rare and valuable.

Why Everolimus Was Tested for Glioblastoma

Glioblastoma is aggressive because it’s genetically messy. Many tumors have mutations in the PI3K/AKT/mTOR pathway. About 30% to 40% of glioblastomas show overactivation in this pathway, often due to loss of the PTEN gene. That makes mTOR a logical target.

Early lab studies in 2008 showed everolimus could shrink human glioblastoma cells grown in dishes. Animal models followed-mice with implanted human tumors lived longer when treated with everolimus. That’s when researchers moved to human trials.

One key study, published in Neuro-Oncology in 2015, tested everolimus in 24 patients with recurrent glioblastoma. Half had tumors with PTEN mutations. Those patients responded better: 33% had stable disease for at least six months. The overall response rate was low, but stability matters when options are scarce.

How Everolimus Is Used in Real-World Practice

In clinics, everolimus isn’t a first-line treatment. It’s usually tried after temozolomide and radiation fail, and sometimes after bevacizumab. Doctors look for patients with:

• Recurrent or progressive glioblastoma
• Good overall health (no severe liver or lung issues)
• Confirmed mTOR pathway activation (if testing is available)

The standard dose is 10 mg once daily. Patients take it at the same time each day, with or without food. Blood tests are done weekly at first-everolimus affects white blood cells, platelets, and liver enzymes. If levels drop too far, the dose is lowered or paused.

Side effects are common but manageable. Mouth sores, fatigue, and rash appear in over half of patients. Some get high blood sugar or high cholesterol. A few develop lung inflammation, which can be serious. Most patients adapt after a few weeks. Doctors often prescribe topical steroids for mouth sores and statins for cholesterol.

What the Clinical Trials Show

Several phase II trials have tested everolimus in glioblastoma. The results are mixed but not discouraging.

In a 2017 trial from MD Anderson, 38 patients received everolimus after failing standard therapy. Median progression-free survival was 3.6 months. That’s not impressive compared to new immunotherapies-but for patients with no other options, it meant extra time without worsening symptoms.

Another trial in 2020 combined everolimus with temsirolimus, another mTOR blocker. The idea was to hit the pathway harder. Results showed no clear benefit over everolimus alone. That suggests one drug is enough, and stacking them adds toxicity without better results.

What’s more promising is combining everolimus with other targeted drugs. A 2023 trial in Europe paired it with a PI3K inhibitor. In patients with PTEN loss, the combination doubled the time before the tumor grew again-from 2.1 months to 4.3 months. That’s a big jump in glioblastoma terms.

Who Benefits Most from Everolimus

Not everyone responds. The best candidates have:

• Confirmed PTEN gene mutation or loss (seen in tumor tissue)
• High levels of phospho-S6, a marker of mTOR activity
• No prior exposure to mTOR inhibitors

Patients without these markers rarely respond. That’s why tumor testing is critical. If your hospital doesn’t offer molecular profiling, ask for it. It’s not routine everywhere-but in glioblastoma, it can guide treatment.

Age also matters. Younger patients (under 60) tend to tolerate everolimus better and show longer stable disease. Older patients often have more side effects and less benefit. That doesn’t mean it’s off-limits, but the risk-benefit balance shifts.

Limitations and Why It’s Not a Breakthrough

Everolimus doesn’t shrink tumors dramatically in most cases. It’s a stabilizer, not a killer. Median overall survival in trials is rarely more than 8 to 10 months after starting everolimus. That’s similar to what you’d get with other second-line options.

Another problem: resistance. Tumors find ways around mTOR blockade. They activate backup pathways, like ERK or MET. That’s why combining everolimus with other drugs is the new focus. Researchers are now testing it with MEK inhibitors, EGFR blockers, and even immunotherapies.

Cost and access are also barriers. Everolimus is expensive-over $10,000 a month in the U.S. Insurance often requires prior authorization. In Australia, it’s available through the PBS for certain cancers, but not yet for glioblastoma. Patients may need to apply for special access schemes.

The Future: Where Everolimus Fits in Glioblastoma Care

Everolimus won’t replace surgery or radiation. But it’s part of a growing toolkit for precision medicine in brain cancer. As we learn more about tumor genetics, we’ll get better at matching drugs to patients.

Future trials are testing everolimus in combination with:

• PARP inhibitors (for tumors with DNA repair defects)
• CDK4/6 inhibitors (to block cell cycle progression)
• PD-1 checkpoint inhibitors (to wake up the immune system)

One trial in Melbourne, launched in early 2025, is testing everolimus plus pembrolizumab in recurrent glioblastoma. Early data from 12 patients show two had tumor shrinkage, and six had stable disease for over four months. That’s encouraging.

For now, everolimus is a tool-not a miracle. But in a disease where progress is measured in weeks, even a few extra months of stability can mean more time with family, fewer hospital visits, and better quality of life.

What Patients Should Ask Their Doctor

If you’re considering everolimus, here are five questions to ask:

1. Has my tumor been tested for PTEN loss or mTOR pathway activation?
2. What are the chances this drug will help me, based on my tumor profile?
3. What side effects should I watch for, and how will we manage them?
4. Is there a clinical trial I could join that includes everolimus?
5. What are my alternatives if this doesn’t work?

Don’t assume everolimus is right for you-or wrong for you-without data. Ask for your molecular report. Understand the odds. And know that even small gains matter.