Abiraterone Vs Enzalutamide: Which Is More Effective for Advanced Prostate Cancer?

When it comes to treating advanced prostate cancer, particularly metastatic castration-resistant prostate cancer (mCRPC), two of the most commonly prescribed medications are Abiraterone and Enzalutamide. Both drugs play crucial roles in slowing down the progression of prostate cancer, but they work in very different ways. While Abiraterone targets testosterone production, Enzalutamide blocks the cancer cells' ability to use testosterone.

Choosing between these two treatments depends on a variety of factors, including the patient’s overall health, the stage of their cancer, and how they respond to side effects. This article will dive deeper into how these drugs work, their effectiveness, side effects, and which might be the better option for certain patients. We will also explore the cost options available in India, where more affordable alternatives to these treatments can offer significant cost savings for patients.

Abiraterone: How It Works

Abiraterone is an androgen biosynthesis inhibitor that prevents the body from making testosterone, the hormone that fuels the growth of prostate cancer cells. Unlike traditional hormone therapies that only reduce testosterone production in the testes, Abiraterone inhibits testosterone production across the body—targeting the adrenal glands and even the cancer cells themselves.

The drug works by blocking an enzyme called CYP17A1, which is involved in producing androgens. Without testosterone, cancer cells lack the fuel they need to grow. However, inhibiting this enzyme also disrupts other hormone systems, leading to potential side effects such as high blood pressure, swelling, and low potassium. To manage these side effects, patients are typically prescribed prednisone to balance hormone levels and prevent the body from overcompensating.

Enzalutamide: How It Works

Enzalutamide, on the other hand, works by blocking the androgen receptor—the docking station on cancer cells where testosterone usually binds. By preventing testosterone from attaching to these receptors, Enzalutamide stops cancer cells from using the hormone to grow, even though testosterone is still being produced.

While Abiraterone inhibits testosterone production, Enzalutamide blocks its ability to fuel cancer growth. This makes it particularly effective in cases of advanced prostate cancer where other treatments have failed. Unlike Abiraterone, Enzalutamide does not require the use of prednisone, making it an option for patients who might be sensitive to steroid use or who wish to avoid the associated side effects.

Effectiveness: Which One Performs Better?

Both drugs have shown promising results in clinical trials, extending survival and delaying the progression of prostate cancer.

Abiraterone has been shown to significantly increase survival rates. In the COU-AA-302 trial, patients who received Abiraterone experienced a median overall survival of 34.7 months compared to 30.3 months for those receiving a placebo. It also doubled the time before the cancer worsened (16.5 months vs. 8.3 months).
Enzalutamide, as seen in the PREVAIL trial, demonstrated a similar effect, with patients showing a median overall survival of 35.3 months, compared to 31.3 months for placebo. Enzalutamide also had an advantage in delaying radiographic progression, showing a radiographic progression-free survival of 20 months versus 5.4 months in the placebo group.

While both drugs perform similarly in extending survival, Enzalutamide may have a slight edge when it comes to delaying disease progression.

Side Effects: Understanding the Risks

Each medication comes with its own set of potential side effects.

Abiraterone's side effects primarily arise from its interference with hormone production. Common issues include high blood pressure, fluid retention, and low potassium. Prednisone helps to manage these, but it brings its own challenges, including weight gain, high blood sugar, and a higher risk of infections. Additionally, Abiraterone can stress the liver, requiring regular blood tests to monitor liver function.
Enzalutamide, while generally easier on the body, can cause cognitive side effects due to its ability to cross the blood-brain barrier. Some patients may experience fatigue, dizziness, or even seizures in rare cases. Enzalutamide has also been linked to increased blood pressure and a slight increase in the risk of heart disease. Memory issues and cognitive impairment have been reported, particularly in older patients.

How They Are Taken

The administration of these drugs differs as well.

Abiraterone must be taken on an empty stomach to ensure proper absorption. Food increases its absorption rate by up to 10 times, which can exacerbate side effects. It is typically taken once daily, but with prednisone prescribed twice a day to manage its side effects. Frequent blood tests are also required to check liver function and potassium levels.
Enzalutamide is easier to take, as it can be taken with or without food, and requires only one daily dose. It does not need the use of prednisone, making it simpler to manage. However, it still requires regular monitoring for neurological symptoms, blood pressure, and possible falls.

Drug Interactions and Contraindications

Abiraterone interacts with enzymes like CYP3A4 and CYP2D6, which can interfere with the breakdown of medications like blood pressure meds, antidepressants, and painkillers. This requires careful dose adjustments. It is also contraindicated in patients with severe liver disease (Child-Pugh Class C), uncontrolled hypertension, or significant heart failure.
Enzalutamide, on the other hand, speeds up the metabolism of certain drugs due to its induction of CYP3A4, CYP2C9, and CYP2C19. This can reduce the effectiveness of medications like warfarin, seizure meds, and some heart drugs. Enzalutamide should be avoided in patients with a history of seizures or neurological issues.

Cost & Availability: Treatment Options in India

In India, the cost of these medications can vary widely depending on whether they are the brand-name versions or generic alternatives. Here are some of the most widely available options:

Zytiga (Abiraterone), manufactured by Johnson & Johnson, typically costs between ₹20,000 and ₹25,000 per month, which is approximately $240 to $300 USD. This is the brand-name version of Abiraterone.
Zelgor (Abiraterone), manufactured by Sun Pharmaceutical Industries Ltd., is a generic version of Abiraterone. It is a more affordable alternative to Zytiga, with prices typically ranging from ₹20,000 to ₹25,000 for a month's supply, providing significant cost savings for patients. This translates to $240 to $300 USD per month.
Xylutide (Enzalutamide), manufactured by Cipla Limited, is an affordable generic version of Enzalutamide. While the brand-name version (Xtandi) can cost up to ₹2,50,000 per month ($3,000 USD), Xylutide is priced much lower at approximately ₹55,000 to ₹65,000 per month ($660 to $780 USD), offering substantial savings compared to the original.

In comparison, the generic versions of Abiraterone and Enzalutamide in India provide significant cost savings. For patients seeking affordable treatment options, choosing generic versions like Zelgor or Xylutide can reduce monthly treatment costs by up to 70%, without sacrificing efficacy.

Which One to Choose: Abiraterone or Enzalutamide?

The choice between Abiraterone and Enzalutamide comes down to the patient’s health status, preferences, and how well they tolerate side effects.

Abiraterone is generally preferred for patients with a history of neurological issues, like seizures or cognitive problems, since Enzalutamide could exacerbate these conditions. It is also used in earlier-stage metastatic prostate cancer, often alongside androgen deprivation therapy (ADT).
Enzalutamide is favored for patients who cannot take prednisone or prefer to avoid its side effects. It is also a strong option for those with non-metastatic castration-resistant prostate cancer (nmCRPC), where the goal is to delay the spread of the disease. Because it doesn't have food restrictions or require steroids, it is often chosen for its convenience.

Conclusion

Both Abiraterone and Enzalutamide are effective treatments for advanced prostate cancer, and each has its unique set of benefits and drawbacks. While Zytiga and Xtandi are the well-known branded options, generic alternatives such as Zelgor and Xylutide offer affordable and equally effective options for patients in India. Ultimately, the decision of which drug to use should be made in consultation with an oncologist, who will take into account the patient's specific needs, health conditions, and how they may respond to side effects. The goal is always to control the cancer while maintaining the patient’s quality of life, all while considering the cost of treatment to ensure the best possible outcome.

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