Answer: Enz abi

Both abiraterone and now enzalutamide are FDA approved in the prechemotherapy setting. My preference will be to administer enzalutamide first. The main reason for my choice is the lack of prednisone and the fact that I administer a lot of immunotherapy in this setting with the goal of suppressing the immune system. Generally, I believe that both drugs are equally efficacious but have differences in side effects that tend to favor enzalutamide, especially because you do not have to administer prednisone with enzalutamide as you do with abiraterone and because of some of the specific toxicities with abiraterone.

The benefit with either enzalutamide or abiraterone administered first after disease progression on ADT will be observed in about 70% to 80% of patients.

With considerations for regulatory or reimbursement issues, we do not yet have enough data available to indicate which of the 2 agents to administer first and how to sequence these agents in this setting. Hence, I do not have any recommendation on sequencing. The benefit with either enzalutamide or abiraterone administered first after disease progression on ADT will be observed in about 40% to 60% of patients.

The majority of the patients I see as a medical oncologist have a high Gleason score and have had a brief duration of response to ADT, and many of these patients will still receive docetaxel as their first-line treatment. About 20% or less of my patients would be real candidates for first-line abiraterone, so these would be patients with low Gleason scores and longer durations of response to ADT. I believe in this group of patients, about 80% would see a benefit with abiraterone.

Answer: Enz abi

Sequencing of enzalutamide and abiraterone depends on factors such as liver function test results, hypertension and other characteristics of the patient, to see if the patient has other underlying diseases, and then one can make a reasonable decision. The need to add prednisone to abiraterone doesn’t frighten us that much, although there is the occasional patient for whom it might make the metabolic syndrome a little bit worse. It’s not common, but certainly from the perspective of a urologist and considering the ease of administration, enzalutamide is a little bit more convenient. With enzalutamide, monitoring does not need to be as aggressive as it does for abiraterone, where you can run into problems with potassium levels and other issues such as heart failure.

As a urologist, I work in a multidisciplinary setting and do not actually prescribe these agents to patients. However, outside of the multidisciplinary setting, I would be more likely to treat with enzalutamide initially rather than abiraterone.

Answer: Enz abi

In this situation, I would sequence enzalutamide first, because it’s not required to be administered with prednisone, neither is it a requirement that the patient take it on an empty stomach.

Answer: Abi enz

Because abiraterone was the first to receive FDA approval, we would sequence abiraterone before enzalutamide.

I have not been satisfied with the responses observed when enzalutamide is used after disease progression on abiraterone. Generally, I have moved on to treat with either radium-223 or chemotherapy. Now that enzalutamide is approved prechemotherapy, I believe more patients will initially receive enzalutamide. However, my sequencing approach will remain as abiraterone first. I do not intend to administer enzalutamide until after chemotherapy. I will treat with abiraterone, perhaps radium-223, chemotherapy, then enzalutamide, in that order.

Currently, we do not know how to select patients who are going to respond better to abiraterone or enzalutamide. It is my belief that a subset of patients will respond better to one than the other. We know this because we see some patients who have primary resistance to these drugs, probably on the order of 10% or so. From the presented data sets, the response rates with these 2 agents are high. However, there is primary resistance to both agents.

We have limited data about sequencing of both agents. The general consensus is if one fails, try the other, which is a reasonable approach. Whichever one is used first, you will not obtain the same type of response with the second choice. Treatment with one of the agents after disease progression on the other results in a more blunted outcome in terms of magnitude and duration of response.

At the molecular level, it’s likely that some patients will be great responders to abiraterone, some will be great responders to enzalutamide and some will respond in sequence. As yet, we simply don’t have the tools available to subselect patients for therapy.

Answer: Enz abi, history of diabetes; Abi enz, history of seizures

If the patient has a history of seizures, my preference will be to administer abiraterone initially. If the patient is diabetic and you don’t want to administer steroids, that patient is a better candidate for enzalutamide first rather than abiraterone. One needs to evaluate the different characteristics of the patients and tailor your treatment choice to the individual.

Answer: Enz abi

I will use enzalutamide first. Enzalutamide is a little bit easier to administer because it is not administered with steroids. However, it is important to note that I have discontinued enzalutamide therapy for more patients than I have with abiraterone. So far, I have only stopped abiraterone therapy for 1 out of 150 of my patients, whereas I have discontinued enzalutamide for a couple of patients because of overwhelming fatigue. Even though enzalutamide does not “crash” the liver or electrolyte levels, it keeps the blood pressure normal and it’s an easy drug to administer, the fatigue associated with it is a real problem. About 10% of my patients experience this overwhelming fatigue on enzalutamide. It is not a cumulative type of toxicity that worsens the longer the patient continues therapy. It’s more like the patient either experiences it or not. In all, I am more likely to discontinue enzalutamide than abiraterone.

Answer: Abi enz

Enzalutamide was recently FDA approved in the mCRPC population prior to chemotherapy. I’ve only used it in clinical trials. I’m the co-principal investigator for the Phase II TERRAIN trial. We have been aggressively and successfully using abiraterone acetate with prednisone prior to chemotherapy since its approval in December 2012. Now that both enzalutamide and abiraterone are approved, I would certainly give some consideration to using enzalutamide either in a primary setting or possibly after the use of abiraterone.