James Luke Godwin, MD
The first-line treatment of patients with metastatic castration-sensitive prostate cancer has undergone a significant number of changes in the last few years. Most recently, the FDA approved abiraterone acetate (Zytiga) in combination with prednisone for patients with metastatic high-risk castration-sensitive disease.
This approval of abiraterone was based on findings from the phase III LATITUDE trial. In the study, there was a 38% reduction in the risk of death with the addition of abiraterone and prednisone to androgen deprivation therapy (ADT) compared with ADT alone.1
Another pivotal trial of abiraterone in prostate cancer was STAMPEDE. This trial showed that the addition of abiraterone to standard initial therapy lowered the relative risk of death by 37% and improved progression-free survival by 71% in both nonmetastatic and metastatic patients with high-risk hormone-naïve disease.2
Although there is much excitement with androgen receptor (AR)-directed agents, docetaxel remains a staple of treatment. James Luke Godwin, MD, says that clinicians have now reached an interesting decision point on how to treat their patients in the frontline setting moving forward.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Prostate Cancer, Godwin, assistant professor, Kimmel Cancer Center Network, Thomas Jefferson University Hospital, recapped recent advancements in frontline metastatic castration-sensitive prostate cancer and highlighted emerging agents with potential in this space.
OncLive: How has first-line treatment for patients with castration-sensitive prostate cancer evolved?
This is a space that has been evolving over the past couple of years. Since 2014 or 2015, we have learned that adding docetaxel upfront provides a survival benefit when added to ADT as opposed to ADT alone. That became a standard of care in 2017, with data from 2 large studies—LATITUDE and STAMPEDE—showing impressive data with the addition of abiraterone to ADT upfront in this setting. Currently, we have good data for 2 separate agents that have different toxicity profiles.
For clinicians, when you meet a patient with metastatic castration-sensitive prostate cancer, it is an interesting decision point. What therapy should clinicians add to standard ADT in the first-line setting? That is an open question.
What are the differences in toxicity profiles between the 2 agents?
Docetaxel is a traditional chemotherapy; it is an old drug that has been used for a very long time. Common side effects include neutropenia, decreased cell counts, fatigue, and neuropathy. The benefit of docetaxel is that you give it for a set time period—only 6 cycles—and then that therapy is complete. You would then continue with ADT alone. Although there is a period where a patient may experience more toxicity, they are only on the therapy for a definitive amount of time. The majority of men in the CHAARTED study, which showed the survival benefit for docetaxel upfront, completed all 6 cycles as planned without dose reduction.
Abiraterone is generally well tolerated. The side effect profile does include some cardiovascular risk and hypertension, which can be managed. However, when considering first-line treatment with abiraterone, you are considering committing a patient to a longer treatment course than with docetaxel. When making that decision, the clinician should work with the patient and consider toxicity, length of treatment, and cost to figure out what works best for that particular patient.
Is there any rationale to look at other agents, such as enzalutamide?
Absolutely, there are trials ongoing looking at enzalutamide in the frontline space. There are the ENZAMET and ARCHES studies. There is also the PEACE1 study, which is looking at a variety of combinations. That trial will have some head-to-head data looking at docetaxel plus ADT versus abiraterone plus ADT, also with or without local radiation therapy dependent on the patient population. There are many subgroups in that study, so that will hopefully add some extra data for us to consider when choosing therapy.