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Treatment Developments Shaking Up Landscape for Nonmetastatic CRPC

Danielle Bucco
Published: Friday, Apr 13, 2018

Mark J. Mann, MD
Mark J. Mann, MD
There have not been designated novel treatment options for patients with nonmetastatic castration-resistant prostate cancer (CRPC) until very recently, explains Mark J. Mann, MD.

State of the Science Summit™ on Prostate Cancer, Mann, an assistant professor of urology at Sidney Kimmel Cancer Center, Thomas Jefferson University Hospital, discussed the developing treatment landscape for patients with nonmetastatic CRPC.

OncLive®: Please provide an overview of your lecture on the treatment of nonmetastatic CRPC.

Mann: The definition of nonmetastatic CRPC is a patient with a prostate-specific antigen (PSA) that is 2 over the nadir, or a 25% increase from the nadir while the testosterone is still repressed. The next part of the diagnosis is determining whether it is metastatic. That is done with a CT scan and a bone scan, which are standard, but there are new imaging modalities that are starting to come into play, specifically PET scans.

The next step in surveillance is to make sure the patient [has] nonmetastatic disease. We discussed the AUA recommendations for treatment, or rather the lack of treatment, and the indication where we will then progress to more advanced treatments. I also discussed the latest ASCO publicized studies, such as enzalutamide in the PROSPER trial and apalutamide in the SPARTAN study.

Can you discuss the current AUA guidelines?

The current AUA guidelines for nonmetastatic CRPC is to continue with ADT. If the patients are not willing or do not accept those recommendations, then you can offer them a first-generation antiandrogen, such as bicalutamide, or a first-generation androgen synthesis inhibitor along with a steroid. The guidelines also are clear that they do not recommend chemotherapy or immunotherapy in those patients.

Can you speak to the importance of the apalutamide approval and the background of the study?

The SPARTAN trial was for nonmetastatic CRPC, where patients could have been clinically N0 or N1, which indicates that they may have had more advanced disease in that trial. This trial randomized patients to apalutamide with ADT or ADT alone. They found that OS endpoints were not met and the time of progression to metastatic disease was approximately 44 months compared with less than 1.5 years in the ADT group alone.

Apalutamide has also recently been added to the National Comprehensive Cancer Network guidelines. Can you discuss this?

Apalutamide is an interesting drug in that it is a nextgeneration androgen receptor inhibitor. It targets the receptor, the signaling cascade, and DNA, binding with fewer central nervous system toxicities.

What are some of the challenges that remain with apalutamide?

It will be interesting to see its efficacy when broken down into racial differentials to determine how effective it is in patients with different ethnicities. Furthermore, it will be interesting to see how it affects the cascade of drugs that typically follows and how it plays into that role.

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