Erleada (Apalutamide) for Prostate Cancer

Erleada (apalutamide) is an oral therapy that was approved in 2018 for the treatment of prostate cancer. It may be used by men with prostate cancer that has not spread (is non-metastatic), but whose cancer is getting worse with only conventional hormone therapy—this is when prostate-specific antigen (PSA) levels are rising rapidly.

The medication works by blocking the androgens (such as testosterone) that cause these cancers to grow and spread, but in a different way than many commonly used hormonal medications.

When combined with hormone therapy, Erleada improves metastasis-free survival, as well as halts the progression of symptoms of the disease by an average of two years compared to treatment with hormone therapy alone. It may also improve survival, but further long-term studies are needed to confirm this.

There are three primary indications or requirements that a person must have in order for Erleada to be used in treatment.

The tumor must not have spread beyond the region around the prostate, meaning there is no evidence of metastases on imaging studies.

The tumor must also have become resistant to standard androgen deprivation therapy (most tumors do become resistant). The kind of therapy tumors may come to resist might include gonadotropin-releasing hormone analogues (GnRH analogue) such as Lupron (leuprolide), Trelstar or Triptodur (triptorelin), Zoladex (goserelin), Vantas or Supprelin (histrelin), or surgery (a bilateral orchiectomy).

Physicians use the term "castration-resistant" to describe tumors that are no longer responding to these therapies.

In addition, those with a high risk of developing metastatic cancer are eligible to try Erleada. Tumors with a PSA doubling time of 10 months or less are more likely to grow and spread.

While not yet approved by the FDA for this use, Erleada may also be beneficial for metastatic prostate cancer that has become resistant to conventional hormonal treatments. Several clinical trials are currently in progress evaluating this use.

The drug should be used cautiously in men who have had neurological problems such as a seizure, brain tumor, stroke, or traumatic brain injury.

There are also some necessary precautions that apply to both a male taking Erleada and any female partner he has if she is or could become pregnant. Men who have a partner who is pregnant will need to use a condom throughout the duration of treatment and for three months after Erleada has been discontinued.

If a partner could become pregnant, birth control that is highly effective should be used throughout treatment and for three months after treatment is completed.

Erleada is a type of anti-androgen therapy referred to as a next-generation androgen receptor blocker. Androgens such as testosterone cause prostate cancers to grow by binding to androgen receptors and stimulating the growth of the tumor.

Erleada effectively blocks the signal that is sent from the receptor to the nucleus of the cell that would cause it to divide and grow. Compared with another drug in this category, Xtandi (enzalutamide), Erleada may have stronger anti-androgen activity and a smaller risk of causing seizures.

In one study of over 1,200 men who met the criteria for treatment outlined above, the average time before the cancer spread was 16.2 months in men who were treated with hormone therapy alone, but 40.5 months in men treated with hormone therapy plus Erleada.

Men treated with Erleada plus hormone therapy were 72 percent less likely to develop metastases (to bones, soft tissue, or lymph nodes outside of the pelvis) or even die due to related complications compared to those not treated with Erleada.

In addition to fewer metastases, men treated with Erleada had fewer symptoms associated with cancer progression than the men not treated with the drug. Even after treatment with Erleada was discontinued, there were apparently some persistent benefits.

Men who experienced the progression of their cancer on Erleada and were then switched to another treatment went a longer period of time before progression occurred on the subsequent therapy than men who did not receive Erleada at all.

As with any medication, Erleada has the potential to cause side effects and complications and may interact with other drugs. When used appropriately, however, only 10.6 percent of men (compared with 7 percent of men treated with a placebo) had side effects severe enough that they needed to stop the drug.

Side effects that occurred more often among people using Erleada than those using a placebo included:

• Rash
• Hypothyroidism
• Fractures

Rashes did resolve for 81 percent of people within two months of onset, however. In regard to hypothyroidism, this occurred in 8.1 percent of people using Erleada vs. only 2 percent of people on the placebo. Fractures, or broken bones, occurred in 11.7 percent of people using Erleada vs. 6.5 percent of people using the placebo.

Other side effects that occurred in 10 percent or more of people using Erleada (but often occur with a placebo as well) include:

• Fatigue
• Diarrhea
• High blood pressure
• Nausea
• Weight loss
• Joint pain
• Hot flashes
• Falls
• Decreased appetite
• Swelling of the ankles (peripheral edema)

If your doctor has recommended Erleada, it's important to understand both the potential benefits and the possible risks of treatment.

Erleada is taken as oral tablets (240 mg total) one time daily with or without food. It should be taken at the same time every day.

It's important to talk to your doctor and pharmacist about all medications you take if you will be using Erleada to check for possible drug interactions. Erleada is a strong inducer of some liver enzymes and has a high potential to interact with a number of different drugs.

Due to the increased risk of falls and fractures, people should be evaluated for the risk of falls and should "fall-proof" their homes. Any evidence of osteoporosis, which would increase the risk of falling, should be noted as well.

It is important if you are taking Erleada to keep in mind certain risk factors.

Erleada can reduce fertility. Men should not donate sperm while being treated with the medication and for at least three months after the treatment is discontinued.

Men who have partners who are or could become pregnant should use condoms throughout treatment and for at least three months after the treatment is stopped.

To check for hypothyroidism, a TSH level should be tested every four months.

Erleada (apalutamide) is a newer treatment for prostate cancer that can significantly reduce the risk of prostate cancer spreading or causing deaths in men whose cancers have not yet spread, have a high risk of spreading, and have become resistant to standard hormone treatments. Fortunately, the treatment appears to be very well tolerated and was not found to reduce quality of life at the same time that it improved survival. Like any medication, however, it's important to be aware of cautions, potential side effects, and drug interactions that might occur while taking the drug.