Precision Medicine in Advanced Prostate Cancer

Alicia K. Morgans, MD, MPH: Hi, and welcome to this OncLive® Peer Exchange titled, “Evolving Management Landscape for Advanced Prostate Cancer.” My name is Alicia Morgans, and I’m an associate professor of medicine in the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago, Illinois. Joining me today in this discussion are my colleagues and friends, Dr Phil Koo, the chief of diagnostic imaging at the Banner MD Anderson Cancer Center in Phoenix, Arizona; Dr Scott Tagawa, the medical director of the GU [Genitourinary] Oncology Research Program at Weill Cornell Medicine in New York; and Dr Sandy Srinivas, a professor of medicine in the division of oncology at Stanford Medicine in Palo Alto, California.

As we are just past the midpoint of 2021, it has been another year stocked with practice-changing advances in the field of GU oncology. In prostate cancer, several recent FDA approvals have been granted. Today, we will discuss evolving approaches that are transforming how we think about precision medicine in prostate cancer, as well as how we’re using systemic therapies for advanced prostate cancer. We’ll focus on the latest research in the context of existing standards of care and highlight practical implications for patient care. Let’s get started on our first topic.

In our first segment, we’ll be talking about how we’re moving toward precision medicine in advanced prostate cancer. Let’s start by thinking about that topic in general. What is precision medicine? And what is precision medicine when we think specifically about prostate cancer? Sandy, what do you think when we think about this particular topic?

Sandy Srinivas, MD: It is individualizing therapies for patients. Our colleagues in lung cancer have done a remarkable job of biopsying after every single therapy, at progression, and tailoring therapy to what an individual needs. It’s been challenging in prostate cancer, given that our patients have predominantly bone disease. The field hasn’t yet completely gone into having a comfort of analyzing tissue from bone. But for the first time ever, we have therapeutics in prostate cancer based on mutations and altered mutations, so we’re getting there.

But there’s tremendous heterogeneity for patients with prostate cancer. Patients respond so differently to the hormonal therapy ADT [androgen deprivation therapy], which we’ve had for decades. Some patients have a dramatic drop in PSA [prostate-specific antigen] and a long duration of response, and then we have others who have barely a couple of months of response, and they progress. There’s such significant heterogeneity that our ability to pick therapy for a given individual should be based on some selection, and that’s what precision medicine means to me.

Alicia K. Morgans, MD, MPH: That’s a great start. As you said, precision medicine goes back to the time of ADT, because targeting the androgen receptor was one of the very first precise ways of targeting a cancer. It’s really interesting to mention that and to also comment on the heterogeneity of this disease.

Scott, what are your thoughts? In prostate cancer and across cancer, we’re trying to move into precision medicine. Where do you feel that stands in prostate cancer? How do you think we can improve on that and target some of that heterogeneity, including things like racial diversity, that we know may be contributing and is a particular challenge in prostate cancer?

Scott T. Tagawa, MD, MS, FACP: I agree, it can be quite complex. Precision medicine, which I would broadly define as the right treatment for the right patient at the right time, is fortunately in play in all fields of medicine, whether it’s internal medicine with diabetes and who needs insulin, etc. There are many more diabetic drugs than when I trained, so I’m glad that we have that help. In a way, precision medicine has been in prime time within prostate cancer for a number of years. We’re further refining it, and it’s true for all stages of disease. With patients with clinically localized, low-risk disease, I’m considering imaging, blood-based and tissue-based biomarkers to help me give the best advice I can in the context of a patient and their comorbidities and wishes for active surveillance vs interventions.

We have moved to much more sophisticated types of diagnostic tools, which nicely has been matched with advanced disease to many more treatment options. Not just ADT, although that’s the backbone for everything, and not just taxane chemotherapy, but we now have a number of different choices, which makes it much more important. One of the relatively new factors in the longer-term scheme of things is germline alterations. If you think about racial disparities, it’s not just germline genomics, exposures, or access to care, it’s a little of all those and much more. There are some factors that look like they may cut across all the other factors, such as a germline BRCA2, but there are others where we need to take all the other factors into account.

Alicia K. Morgans, MD, MPH: I couldn’t agree more. To comment on germline and somatic mutations, these are things we can target at this point with a couple of FDA-approved therapies, including our PARP inhibitors, and we have things like BRCA2, as you mentioned. Sandy, are you thinking about other alterations at all, like tumor mutational burden or MSI [microsatellite instability]-high status, when you’re seeing patients with very advanced prostate cancer? That would also be a way to enact precision medicine, right?

Sandy Srinivas, MD: Totally. Immunotherapy has been such a welcome change in so many different cancers. In prostate cancer, just monotherapy with checkpoint inhibitors hasn’t been that promising, so we’re fortunate to have FDA approval for pembrolizumab, for instance, which has an approval across all cancers for tumor mutational burden greater than 10 and for MSI-high. I’ve looked very hard, and I can’t tell you the number of times that, especially for patients post-AR [androgen receptor] therapy, where you’re looking for something besides chemotherapy. It’s at that point that I’ve definitely looked at prior tissue and liquid biopsies, but I haven’t yet found that patient who has MSI-high. But certainly, that’s a time to look for these markers, because those patients who have this will have such an amazing therapeutic option where they could have a response that could be more long-lasting.

Alicia K. Morgans, MD, MPH: Absolutely. It’s only 1% to 3% of our patients who are going to have that MSI-high status, and that’s in the mCRPC [metastatic castration-resistant prostate cancer] setting, so these are truly patients who are needles in a haystack. I have 1 patient who I inherited from someone, but haven’t identified any on my own, despite testing as much as I possibly can, just as you mentioned. But despite this being a rare situation for our patients, it’s absolutely imperative that we identify those patients if they’re in our practices, because there can be an option in pembrolizumab.

Transcript Edited for Clarity