Daniel J. George, MD: I want to shift gears to therapy and consider our earlier use of chemotherapy and novel androgen receptor–targeted therapy in the metastatic castration-sensitive prostate cancer setting. Those agents have really changed the landscape of not just castration-sensitive disease, but the biology that emerges in castration-resistant disease.
Eleni, I was wondering if you could walk us through some of the data regarding the rationale for chemotherapy. I want to address some of the updated data from CHAARTED, some of the rationale for abiraterone from STAMPEDE and LATITUDE, and then some of the newer studies that have been coming out around enzalutamide, apalutamide, and others. Where are we today with the management of metastatic castration-sensitive prostate cancer?
Eleni Efstathiou, MD, PhD: Thank you, Dan. Before we go into that, I want to add a comment on the previous topic. Tanya, great comment. A lot of us are trying to do studies along these lines. Ben, I liked your attitude about knowledge offering the way forward. There are a lot of naysayers still saying we won’t be able to use it. The bottom line is that none of us has had this extensive experience that we’re seeing in the rest of the world. We need to look more toward Europe and Germany, where they all started to understand better how they’re actually using it.
One thing that Chuck might come back to later when we speak about the Hoffman data is that with the PSMA [prostate-specific membrane antigen] PET [positron emission tomography], we get a lot of specificity. We’re going up to 95%, but we’re still not there with sensitivity. That’s what I’m going to use to segue into the hormone-naïve castration-sensitive space with regard to heterogeneity. It could be that PSMA, being a more molecular-based imaging assay, is not picking up the disease to the extent that we want because of that heterogeneity.
With that in mind, I think we’re very privileged, compared with even 5 years ago, to have this option right now in the clinic for what is metastatic castration-sensitive disease. Even though we’ve had these data—starting from 2014 or 2015 with CHAARTED, STAMPEDE, LATITUDE, and TITAN, and are waiting on other data sets like ARASENS to come forward—the problem we’re having is a disconnect with real-world practice.
Even in this country, where abiraterone has become generic, the numbers may be a little skewed, but they don’t look like we’re reaching even 50% capacity in treating these men with castration-naïve disease with any of these agents. The numbers for chemotherapy are actually quite low at less than 10%, and Ben Lowentritt might want to comment on that. We have strong data to support that the use of cytotoxic chemotherapy in the name of docetaxel or any of 3 FDA-approved agents—abiraterone, enzalutamide, apalutamide—has an impact in all primary end points, including RPFS [radiographic progression-free survival] and overall survival, and all secondary end points.
Why are we not using them yet? Is it part of the learning curve? Is it part of the difficulties of access in the clinic? Are there still those who believe that later may be equivalent to earlier? That’s my main point. Given all these trials—especially when you look at 11 positive phase 3 trials with enhanced androgen signaling inhibition for pointing to the fact that it’s 1 of the main drivers—it should probably be your first choice with exceptions that we can comment on. Earlier is better, and we’re going to get to this data.
This is my main concern. We’re all embracing the fact that we can treat hormone-naïve disease regardless of risk or volume. We should take into consideration the comorbidities that may be impacting the quality of life of these patients. We are now understanding better how to cater to bone health, and a lot of you were doing research along the lines of generalized health index. My main concern is, where are we standing with actual real-world practice?
Charles Ryan, MD: If I could comment, Dan. Eleni touched on this also. Part of what we’re trying to do is attach a binary tool to a continuous variable, and that metastatic disease is probably a continuum. Eleni mentioned the sensitivity of the gallium Ga 68 PSMA PET not being as high as we would like. That’s because it’s higher: The higher the PSA [prostate-specific antigen] gets, we don’t really need it. Where we really want to have it is when it begins to lose a bit of its sensitivity, but the idea that we go from having no metastases to some metastases as if we’ve jumped over some border is not really the case. They’re always there. It’s just a matter of the volume.
Daniel J. George, MD: It’s a great point, and our coding makes everything black-and-white, but the reality is that we see this disease as a continuum.
Transcript Edited for Clarity