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Posadas Breaks Down Rapidly Evolving Prostate Cancer Paradigm

Brandon Scalea
Published: Thursday, Mar 07, 2019

Dr. Edwin Posadas
Edwin Posadas, MD
Researchers are tapping into new treatment strategies with a focus on quality of life for patients with prostate cancer; however, oncologists still only have a surface-level understanding of the biology of the disease, said Edwin M. Posadas, MD, FACP.

Among the most highly anticipated findings presented at the 2019 Genitourinary Cancers Symposium were the results from the phase III ARAMIS trial, which examined the addition of darolutamide to androgen deprivation therapy (ADT) versus placebo plus ADT in patients with nonmetastatic castration-resistant prostate cancer (CRPC). At a median follow-up of 17.9 months, metastasis-free survival was significantly prolonged with darolutamide compared with ADT alone at 40.4 months versus 18.4 months, respectively (HR, 0.41; 95% CI, 0.34-0.50; P <.0001).

Median overall survival was not reached in either arm, but data showed that darolutamide was associated with a 29% reduction in the risk of death versus the control arm (HR, 0.71; 95% CI, 0.50-0.99; P = .0452).

A central focus of this study was to establish the risk–benefit ratio of darolutamide compared with the FDA-approved androgen receptor (AR) inhibitors enzalutamide (Xtandi) and apalutamide (Erleada). Data from ARAMIS indicated a favorable safety profile, with no increase in adverse events (AEs) and a median time to pain progression of 40.3 months compared with 25.4 months in the placebo arm (HR, 0.65; 95% CI, 0.53-0.79; P <.0001).

Based on these findings, a new drug application was filed with the FDA in February 2019 for darolutamide for the treatment of patients with nonmetastatic CRPC.

“Prostate cancer is a field in evolution right now,” said Posadas, medical director of the Urologic Oncology Program at Cedars-Sinai Medical Center. “Our knowledge of the biology of the disease is moving so fast, but we still have a long way to go.”

In an interview with OncLive, Posadas discussed recent prostate cancer data and shed light on where emerging therapies may fit into this landscape.

OncLive: What were the biggest takeaways you had from the prostate cancer data that were presented at the 2019 Genitourinary Cancers Symposium?

Posadas: The prostate cancer session had a lot of great work in several important areas. One of the big ones [focused on] AR-targeted therapies. We saw updated data with drugs we already know, such as enzalutamide, but we got a nice look at some of the initial clinical data with darolutamide—this information has been anticipated by the field. We also had a nice little taste of what has been happening with PARP inhibitors [in this space]. There is, of course, the immunotherapy question that remains unanswered at this time.

The other nice thing about the prostate cancer updates was that there is a lot of brewing biology. You are seeing it in the form of imaging studies that are being done. For example, PET-imaging studies, which have different conjugates attached to them, such as prostate-specific membrane antigen (PSMA), which has been a hot imaging agent and therapeutic.

Then, there is the idea of looking at different biological phenotypes. We heard a nice discussion about the use of the PAM50 classifier historically being brought into the breast cancer space. The relevance of that general theme is important in prostate cancer and it’s where we will select therapies for patients, including [AR-targeted] drugs as well as PARP inhibitors. We are in for a lot.

Where do you see darolutamide fitting into the treatment paradigm?

There are a couple of important things that came out of the ARAMIS trial. First, the bar was set pretty high. With enzalutamide and apalutamide already available and used by most clinicians at this point, darolutamide had to demonstrate that it was just as active [as those agents]. That bar was very clearly met, and I do not think anyone left the presentation hall thinking darolutamide was “a day late and a dollar short” in terms of activity.

Some data that were emphasized were interesting, and a lot of data were actually underemphasized. It was nice that we got to see the chemical structure of the drug, and it became very clear to us that this is a very different molecule—that is important. [It has been] emphasized that it has a lack of penetration into the central nervous system, which will hopefully drive down toxicity; the data seem to support that so far. As more data come in with these larger trials—TITAN is down the road—it will be interesting to see how the toxicity matters will play out, especially in a sicker patient population.


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