In advanced prostate cancer, androgen deprivation therapy (ADT) has been a mainstay of treatment for more than fifty years. The details of ADT are discussed here if you'd like to learn more. In the past decade or so, physicians who treat advanced prostate cancer have come to understand that, in a variety of clinical scenarios, ADT alone is not enough. As a result, other treatments are now being added to ADT in so called “treatment intensification”. While chemotherapy was the first to be added to ADT, so-called novel hormonal therapies (NHTs; also known as androgen receptor-axis-targeted therapies (ARATs)) are more commonly used for most patients today. While ADT effectively decreases the testosterone within the body that drives prostate cancer growth, the success of these treatments clearly shows that targeting of testosterone-driven pathways has benefit in advanced prostate cancer.

Following the introduction of abiraterone and enzalutamide, further related medications have become available. One such medication is apalutamide. Apalutamide, like enzalutamide, acts to block the action of testosterone by affecting the androgen receptor. It blocks the androgen receptor’s ability to carry out its functions in a variety of ways including blocking its movement within the cell, blocking its ability to interact with DNA, and blocking its ability to create signals within the cell. In this mechanism, apalutamide acts as a more potent version of prior anti-androgens such as bicalutamide.

Who might be prescribed Apalutamide?

Apalutamide is approved, and has demonstrated survival benefits, for men with advanced prostate cancer in two difference scenarios. First, in men with non-metastatic castration resistant prostate cancer (nmCPRC; in which in apalutamide will be started after the PSA is going up even though the testosterone is low while on ADT and there are no sites of metastasis on imaging), the SPARTAN study showed the using apalutamide reduced the risk of men developing metastases by 72%. Further, even though men who developed metastases received additional treatment at that time, starting apalutamide early before the metastases developed (at nmCRPC) reduced the risk of death by 22%.

Apalutamide may also be used in men with metastatic castration sensitive prostate cancer (mCSPC; where apalutamide will be started concurrently or shortly after ADT). In this setting, the TITAN trial showed that using apalutamide with ADT, as compared to ADT only, reduced a man’s risk of death by 35%.

Patients who should not take Apalutamide

There are limited reasons why patients should not take apalutamide. Men with a history of seizures, who have had a stroke, those with prior brain injuries, and those whose cancer has spread to the brain may not be well suited to taking apalutamide. Additionally, patients with an allergy or hypersensitivity to apalutamide should not receive it.

As always, let your physician know if you have heart or kidney problems.

Instructions for taking Apalutamide

Apalutamide is prescribed at four tablets to be taken each day. These should be taken at the same time each day and may be taken either with or without food.

Apalutamide may have effects on other medications that you are taking. As your physician discusses treatment options for advanced prostate cancer, ensure that they are aware of all of the other medications that you are taking. Further, a cancer pharmacist can be very helpful in ensuring that there are not harmful interactions between taking multiple medications.

Side effects of Apalutamide

There are both common (and often relatively mild) and uncommon (and sometimes severe) side effects. Among the more common side effects are significant fatigue (tiredness), high blood pressure, nausea, diarrhea, and heart disease. A notable risk of apalutamide that is less common for other similar medications is rash. This can often be treated with creams but sometimes requires other oral medications to treat. Patients taking apalutamide may also have issues with thyroid function that require them to take thyroid-replacement pills and may have an increased risk of falling and breaking bones (fractures). Other side effects include muscle pains, diarrhea, and constipation. There is a small increased chance of having a seizure for men taking apalutamide. This risk is higher if you have had seizures before, drink a lot of alcohol, have other health problems that affect the brain (a stroke before, head injuries, or cancer spread to the brain), or are taking medications that make seizures more common. Numerous other side effects are possible and may be related to apalutamide treatment.

As always, the articles on this site should not constitute specific medical advice. Discuss the specifics of your clinical situation and your treatment options with your physician.

Zachary Klaassen, MD, MSc
Urologic Oncologist, Georgia Cancer Center, Augusta University, Augusta, GA, USA