First-Line Options in Metastatic Castration-Resistant Prostate Cancer

First-line options for treating metastatic castration-resistant prostate cancer (mCRPC) were debated throughout the annual meeting of the American Urological Association (AUA). In this exclusive MedPage Today video, Alicia Morgans, MD, MPH, medical director of the survivorship program at Dana-Farber Cancer Institute in Boston, discusses first-line therapy for mCRPC and her approach to deciding between different treatment options.

Following is a transcript of her remarks:

Remembering of course that we are going to try to intensify for all patients with metastatic hormone-sensitive disease, our patients are going to have been exposed to more than just ADT [androgen deprivation therapy] alone by the time they hit first-line mCRPC status, for most patients. And they may of course come in through a non-metastatic CRPC pathway as well, again with intensified treatment. Because of that, it’s really critical to recognize what a patient has had before and try to switch mechanism of action, particularly if that patient has had intensified therapy with an AR [androgen receptor]-targeted agent. Because back-to-back — or even an AR targeted agent, chemo, AR-targeted agent — really gives us very little benefit from that second AR-targeted agent. In multiple phase III clinical trials where a second AR-targeted agent was the control arm, if you will, the median time to progression was somewhere around 2.5 to 3.5 months. So that’s really giving us very little, even if we see a brief PSA [prostate-specific antigen] response, we’re not going to meaningfully change the trajectory of the disease for the majority of patients. So that’s just really, really important.

So if we’re changing mechanism of action, how do we choose well for asymptomatic patients, minimally symptomatic patients. Maybe we think about something like [sipuleucel-T (Provenge)]. For patients who have visceral crisis, cord compression, something that is really dramatically an event that’s rapidly progressive, chemotherapy is still probably the best approach. And if a patient has bone-only metastatic disease and has some symptomatology, even if that’s just an anemia or some mild fatigue, then radium can be an option there as well. We can’t use things necessarily like lutetium-[177] in that setting yet.

One other thing I should mention, this is all of course based on Dr. Gomella’s [Leonard Gomella, MD] fantastic counseling about germline and somatic testing, we might be able to use PARP inhibitors in this setting for patients with [homologous recombination deficiency] mutations, as well as pembrolizumab [Keytruda] for patients who have [microsatellite instability]-high status. So thinking about those, and ensuring that we kind of really view that entire landscape is important for first-line mCRPC.