Deborah A. Bradley, MD, medical oncologist, Levine Cancer Institute, Atrium Health, discusses the adverse events (AEs) that are associated with enzalutamide (Xtandi) and apalutamide (Erleada) in prostate cancer.

In the phase III PROSPER and SPARTAN trials with enzalutamide and apalutamide, respectively, fatigue was a common AE, says Bradley. This event may be due, in part, to the antiandrogens, as most patients with prostate cancer experience fatigue; it may be compounded by the use of androgen deprivation therapy, which lowers testosterone.

Additional AEs associated with apalutamide include rash, hypertension, and risk of falling, says Bradley. These agents have enhanced central nervous system penetration, which resulted in a greater rate of falls in the trials. However, since this was observed in both groups, it has been hypothesized that risk of falling is just associated with the patient population. As patients get older and have more comorbidities, they are more likely to fall. Investigators are hoping to clarify this relationship with further research, concludes Bradley.

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Dr. Bradley on Adverse Events Associated With Enzalutamide and Apalutamide in Prostate Cancer

Deborah A. Bradley, MD, oncologist, Levine Cancer Institute, Atrium Health, discusses next steps for research in nonmetastatic prostate cancer.

The SPARTAN and PROSPER trials moved the needle in the right direction for this treatment paradigm, which had remained stagnant for some time. A couple of important unanswered questions that need to be addressed in future research is if apalutamide (Erleada) and enzalutamide (Xtandi) should be combined with other agents and if one agent demonstrates superiority over the other. Bradley says that in her opinion, one is not more effective than the other.

In the SPARTAN trial, there was an exploratory secondary endpoint, which looked at a second disease-free survival. Bradley says the patients who received apalutamide and then moved on to another therapy did better compared with those who received placebo before the next phase of treatment. This brings up the question of when to treat patients—is sooner better?

Additionally, when patients with metastatic castration-resistant prostate cancer switch from an agent like apalutamide to abiraterone acetate (Zytiga), or vice versa, there is no significant benefit. But when patients are treated first in the nonmetastatic setting, they seem to have a better response, Bradley says. Future research is needed to better understand why patients might respond in one situation and not the other.

Deborah A. Bradley, MD, oncologist, Levine Cancer Institute, discusses next steps for research in nonmetastatic prostate cancer.

Dr. Bradley on Next Steps for Research in Nonmetastatic Prostate Cancer

Deborah A. Bradley, MD, medical oncologist, Levine Cancer Institute, Atrium Health, discusses the importance of exercise in the management of prostate cancer treatment-related adverse events (AEs).

An area of prostate cancer that Bradley says needs more research is in terms of AE management for prostate cancer survivors. A lot of patients become very fatigued while undergoing therapy, and getting them up and exercising is an important way to overcome this. It is widely known that a common AE associated with chemotherapy is fatigue, but more work needs to be geared toward this. Bradley stressed that as therapy becomes more advanced, patient quality of life is a necessary important endpoint in clinical trials.

Additionally, as these therapies are moved into earlier settings, cardiac toxicity could become a factor. If a patient’s testosterone is being suppressed for such an extended period of time, researchers have to better understand the long-term AEs that could occur. Proper exercise regimens could be crucial here, as well.

Deborah A. Bradley, MD, medical oncologist, Levine Cancer Institute, Atrium Health, discusses the importance of exercise in the management of prostate cancer treatment-related adverse events.

Dr. Bradley on Exercise in Treatment-Related AE Management

Deborah A. Bradley, MD, medical oncologist, Levine Cancer Institute, discusses the impact of the recently published SPARTAN and PROSPER trials in nonmetastatic castration-resistant prostate cancer (CRPC).

 When enzalutamide (Xtandi) and abiraterone acetate (Zytiga) were shown to improve overall survival in the metastatic setting, researchers hypothesized that if patients with metastases benefit, so should patients without metastases. However, there were never data to support this until the phase III SPARTAN and PROSPER trials. These studies had very similar designs and looked at 2 agents, enzalutamide and apalutamide (Erleada). Primary endpoints in both trials were metastasis-free survival, and both agents significantly prolonged this endpoint. This benefit was seen across all subgroups, Bradley adds.

 These findings led to the FDA approval of apalutamide and enzalutamide in February 2018 and July 2018, respectively. Bradley concludes that not only is it important to have 2 treatment options in this space, but also 2 clinical trials to prove their efficacy.

Deborah A. Bradley, MD, medical oncologist, Levine Cancer Institute, discusses the impact of the recently published SPARTAN and PROSPER trials in nonmetastatic castration-resistant prostate cancer.

Deborah A. Bradley, MD

Articles

Dr. Bradley on Adverse Events Associated With Enzalutamide and Apalutamide in Prostate Cancer

Dr. Bradley on Next Steps for Research in Nonmetastatic Prostate Cancer

Dr. Bradley on Exercise in Treatment-Related AE Management

Dr. Bradley on Impact of SPARTAN and PROSPER in Nonmetastatic CRPC