These different drugs were approved around the same time and have very different mechanisms of action. What we’re seeing already is the shift toward the earlier use of all of these treatments. In metastatic hormone-sensitive prostate cancer (mHSPC), we’re now using docetaxel chemotherapy. That’s an example of how we’re bringing more systemic therapies earlier into the disease course.

There are ongoing clinical trials looking at the use of androgen receptor (AR)-targeted therapies in M0 patients, that is, patients without metastatic disease who have CRPC. The question is, for example, when should we be using sipuleucel-T? Obviously, we’ve always talked about this approved immunotherapy being used in asymptomatic patients with mCRPC, but early in the disease course.

And we talk about how radium-223 should probably be used earlier than we typically have been using it, which is often at the very end of life – in which case, it really probably wouldn’t have the same level of benefit. I think that this is a struggle we’re having because we don’t have level 1 evidence about the optimal sequence, and it is likely that the optimal sequence is going to be different from patient to patient. We have to remember that there are going to be specific scenarios in which certain drugs may be particularly valuable.

The AR pathway may be very valuable in a large subset of CRPC patients. However, in some patients, they may blow through AR-targeted therapies because the androgen pathway may not be the main driver of their progression. Those patients may need to be switched earlier to chemotherapy, for example, if they had a very short primary response to ADT or primary androgen deprivation. Certainly, if someone has a very short response to one AR-targeted therapy like abiraterone or enzalutamide, then it doesn’t always make sense to switch to the other, which is something that I know a lot of clinicians do. It’s just something that we’re still figuring out in terms of prognostic markers. I think it’s important to look at the totality of what our choices are for a patient. We have to think about using these drugs earlier, but also try to be as rational as possible about which drug to use, in which sequence, and really to try to benefit patients by not waiting until they’re so symptomatic and so late in their course that they’re not going to benefit from the drug.