Abiraterone Vs Enzalutamide: Which Is More Effective?
Abiraterone and Enzalutamide are two common treatments for advanced prostate cancer. Both work to slow down or stop the cancer, but they do it in different ways.
One targets testosterone production, the other blocks testosterone from affecting cancer cells. Which one to choose depends on the patient’s overall health, how the cancer is progressing, and how they handle side effects.
This post looks at both drugs and compares how they work, their side effects, and when one might be a better option than the other.
Abiraterone: Basic Overview
Abiraterone stops the body from making testosterone, which cancer needs to grow. It can cause side effects like high blood pressure, so patients take prednisone. It’s used for advanced prostate cancer that doesn’t respond to other treatments.
Enzalutamide: Basic Overview
Enzalutamide blocks cancer cells from using testosterone. It’s used for advanced prostate cancer and helps delay cancer spread, especially for patients with rising PSA levels but no visible cancer.
A Detailed Comparison Between Abiraterone vs Enzalutamide
Now, here are more details about both drugs and how they compare with each other.
How They Work
Abiraterone stops the body from making testosterone. Not just in the testes, like most hormone therapies, but everywhere; adrenal glands, even the cancer cells themselves.
It shuts down an enzyme called CYP17A1, which is vital for making androgens (male hormones). No testosterone, no fuel for the cancer. But there’s a catch. Blocking this enzyme also messes with other hormones, like mineralocorticoids, which control salt and water balance. That can cause high blood pressure, swelling, and low potassium.
So, patients take prednisone to stop the body from freaking out and overproducing stress hormones.
Enzalutamide works differently. It doesn’t stop testosterone from being made—it just makes sure the cancer cells can’t use it. It blocks androgen receptors, the little docking stations inside cells that testosterone normally attaches to. No signal gets through, so no growth.
1. What They Treat
Both are for advanced prostate cancer that doesn’t respond to traditional hormone therapy (metastatic castration-resistant prostate cancer, or mCRPC). But Abiraterone is also used in earlier-stage metastatic cancer that still responds to hormone therapy (mCSPC).
Enzalutamide has an even broader reach. Besides mCRPC and mCSPC, it’s approved for non-metastatic castration-resistant prostate cancer (nmCRPC), which is cancer that hasn’t spread but refuses to stop growing. Some doctors prefer it in cases where the main goal is buying time before the cancer spreads.
The PROSPER trial showed it delayed metastasis in high-risk patients, which makes it useful for people with rising PSA levels but no visible cancer on scans.
2. Effectiveness
Both drugs extend survival, slow cancer down, and help patients stay off chemotherapy longer. The COU-AA-302 trial found Abiraterone pushed overall survival to 34.7 months versus 30.3 months with placebo. It also nearly doubled the time before cancer got worse (16.5 months vs. 8.3 months).
Enzalutamide performed similarly in the PREVAIL trial: 35.3 months vs. 31.3 months overall survival, with radiographic progression-free survival at 20 months vs. 5.4 months. A slight edge over Abiraterone when it comes to delaying progression, but in real-world practice, the two are pretty close.
3. Side Effects
Abiraterone’s side effects are mostly from messing with hormones. Because it blocks CYP17A1, it causes high blood pressure, fluid retention, and low potassium. To fix this, prednisone is required.
But prednisone has its own baggage: weight gain, high blood sugar, increased infection risk. Abiraterone also stresses the liver, so blood tests are needed to catch any damage early.
Meanwhile, Enzalutamide can cross into the brain, which means it sometimes causes dizziness, fatigue, or even seizures in rare cases. That makes it a bad choice for people with epilepsy, strokes, or brain injuries. It also raises blood pressure and might slightly increase heart disease risk over time.
Compared to Abiraterone, it causes more cognitive issues but fewer heart-related problems. It has been linked to memory issues in some people, though how much that matters depends on the patient.
4. Administration
Abiraterone is tricky. It must be taken on an empty stomach because food increases absorption by up to 10 times, making side effects way worse. It’s taken once daily, plus prednisone twice a day to manage side effects. Patients also need frequent blood tests to check liver function and potassium levels.
Enzalutamide is simpler. Once a day, with or without food. No steroids. But it still requires monitoring, especially for neurological symptoms, blood pressure, and falls. Some doctors check cognitive function over time, especially in older patients.
5. Drug Interactions
Abiraterone interacts with CYP3A4 and CYP2D6, enzymes that help break down medications. It can interfere with blood pressure meds, antidepressants, and painkillers, so doctors need to adjust doses carefully. Liver problems make this worse.
Enzalutamide speeds up drug metabolism because it induces CYP3A4, CYP2C9, and CYP2C19. This means it reduces the effectiveness of warfarin, seizure meds, and some heart drugs.
Anyone on multiple meds needs a careful review before starting Enzalutamide.
6. Contraindications
Abiraterone is contraindicated in patients with severe liver disease (Child-Pugh Class C) because it can cause liver enzyme levels to rise dangerously high. It is also avoided in patients with uncontrolled hypertension or significant heart failure, as its effects on mineralocorticoids can worsen these conditions.
Enzalutamide should not be used in patients with a history of seizures or neurological disorders, as it lowers the seizure threshold. Patients with stroke risk, significant cognitive impairment, or balance issues may also be poor candidates due to its CNS-related side effects.
7. Cost & Availability
Abiraterone price is significantly cheaper than Enzalutamide, thanks to being more widely available as a generic.
Although, the added cost of prednisone and frequent lab monitoring can make long-term treatment more expensive than it initially appears.
Enzalutamide remains brand-name only, making it more expensive upfront. However, because it does not require prednisone or frequent monitoring, its total cost of treatment may be comparable to Abiraterone in some cases, even despite the higher Enzalutamide price.
Insurance coverage varies, so financial considerations also may influence drug selection. Apart from these, patients also worry whether the treatment of prostate cancer can cost a lot of money?
8. Quality of Life
Abiraterone has more daily hassles: strict food rules, prednisone side effects, frequent monitoring. But it’s generally well-tolerated if those issues are managed.
Enzalutamide is easier in some ways: no steroids, no food restrictions. But for some, the fatigue and brain fog are deal-breakers, especially if they need to stay sharp for work or daily tasks.
Older patients, in particular, might struggle more with Enzalutamide’s effects on energy and balance.
9. Future Research & Trials
Ongoing studies are exploring ways to improve Abiraterone’s effectiveness, with a focus on therapeutic drug monitoring (TDM).
Research has shown that higher plasma levels of Abiraterone are linked to better outcomes. For example, monitoring drug levels and adjusting doses can reduce side effects and improve survival, as shown in studies published in Nature Cancer and The Journal of Clinical Oncology.
Researchers are also testing combinations of Abiraterone with other therapies. The MAGNITUDE trial has shown that pairing Abiraterone with Niraparib can improve progression-free survival in patients with BRCA mutations. The STAMPEDE trial has confirmed that adding Abiraterone to standard treatments for high-risk prostate cancer improves overall survival.
These findings point toward combining Abiraterone with other drugs or adjusting its dosage to achieve better outcomes for mCRPC patients.
When Is Abiraterone Used Over Enzalutamide?
Abiraterone is the better choice for patients who have a history of seizures, cognitive problems, or neurological issues since Enzalutamide can make these worse. It’s also commonly used for metastatic hormone-sensitive prostate cancer, especially when combined with standard androgen deprivation therapy (ADT) to improve survival outcomes.
When Is Enzalutamide Used Over Abiraterone?
Enzalutamide is preferred for patients who can’t take prednisone or want to avoid its side effects. It’s also a good option for non-metastatic castration-resistant prostate cancer to help delay the spread of the disease. Since it doesn’t have food restrictions and needs less monitoring, it’s usually chosen for convenience.
Conclusion
Both Abiraterone and Enzalutamide do a good job at treating advanced prostate cancer. Which one works best really depends on the patient: their health, how they live day-to-day, and how well they can deal with side effects. Each drug targets different things, but at the end of the day, it’s about what fits the person. Your oncologist can prescribe according to the patient's condition. The goal is to control the cancer and help the patient feel as good as possible.
