Clinical Scenario 1: A 67-Year-Old With Metastatic HSPC


Centering discussion on a clinical scenario of metastatic hormone-sensitive prostate cancer, expert panelists consider how they might approach frontline therapy in this setting.


Evan Y. Yu, MD: Hello, and welcome to this OncLive® Peer Exchange, developing strategies for the treatment of prostate cancer. I'm Dr Evan Yu. I'm at the Fred Hutch Cancer Center at University of Washington in Seattle. I'm joined today by a panel of my colleagues who also treat prostate cancer. I'd like to welcome them. We have Dr Andrew Armstrong. Please go ahead and introduce yourself.

Andrew J. Armstrong, MD, MSc: Hi. Andy Armstrong. I'm a medical oncologist, professor of medicine, pharmacology, cancer biology, medical oncologist at Duke [Durham, North Carolina] and the Duke Cancer Center for prostate and neurologic cancers.

Evan Y. Yu, MD: Great. Dr Pedro Barata.

Pedro C. Barata, MD, MSc: Thank you for having me. I'm Pedro Barata. I'm a GU [genitourinary] medical oncologist and assistant professor of medicine at Tulane Medical School in New Orleans, Louisiana.

Evan Y. Yu, MD: Dr Tanya Dorff.

Tanya B. Dorff, MD: Hi. I'm Tanya Dorff. I'm the section chief for genitourinary medical oncology at City of Hope, [Duarte, California].

Evan Y. Yu, MD: And Dr. Mary-Ellen Taplan.

Mary-Ellen Taplin, MD: Hello. Thank you, Evan. Dr Mary-Ellen Taplan. I'm a professor of medicine at Dana-Farber Cancer Institute in Boston, Massachusetts.

Evan Y. Yu, MD: Thanks so much, it's wonderful having you all here today. Let's get started on our first topic today. We're going to discuss some clinical scenarios that are relevant to patients with advanced prostate cancer. Of course, we will bring in some new data that's just been presented at ASCO [American Society of Clinical Oncology] here. The first case is 67-year-old gentlemen who presents with increased urinary frequency and intermittent low back pain. His past medical histories completely unremarkable. He undergoes a digital rectal exam that demonstrates an enlarged prostate. His PSA [prostate specific antigen] is found to be 44.3 nanograms per milliliter (ng/mL) and a bone scan is performed which demonstrates 2 bone metastases in the vertebral spine, 2 in the left pelvis, and 1 in the left femur. Treatments initiated with androgen deprivation therapy plus 6 cycles of docetaxel chemotherapy, which is very-well tolerated by the patient. The PSA decreases to 0.25 ng/mL. I'm going to ask Dr Tanya Dorff first with this first question. I want to know your thoughts on this scenario. How this patient presented, how this patient was treated. What are your thoughts on this? Is this something you typically see in your clinic?

Tanya B. Dorff, MD: Yes. We do see some of these patients unfortunately who are already metastatic at diagnosis, and we know they have a little bit more aggressive disease course. Because he had high volume disease with 4 or more bone metastases with 1 outside the axial skeleton, which was a charted definition- or visceral metastases qualifies as well, but he did not have that. It was appropriate to consider docetaxel. However, now that we've seen the triplet data from PEACE1 and ARESENS, we know that it's important to have that AR [androgen receptor] targeted agent as well, even if you're using docetaxel. The one thing that maybe I would have done differently is also using an AR targeted agent. Then, what spooks me is when patient has a relatively low PSA for a high disease volume. That can be associated with more aggressive behavior as well. Then with the long bones, when they're involved, I want to make sure there's nothing that could be an impending pathologic fracture and take an extra look at that and make sure we're giving bone support.

Evan Y. Yu, MD: Excellent. You mentioned some of the treatments that could be used. Now, I'm going to ask Dr Armstrong here. Obviously, you were the PI for the ARCHES trial. Why don't you review that study and other options that could be used for this patient in this scenario?

Andrew J. Armstrong, MD, MSc: Yes. Thanks, Evan. There are many winners in this scenario. What we call a winner is a drug that has Level 1 evidence that it improves survival. Enzalutamide based on both the ENZAMET and ARCHES data suggests better survival with a potent AR inhibitor when used early as opposed to waiting for castration resistance to develop. The same would be said of darolutamide and abiraterone. The triple therapy that Tanya mentioned is an emerging option, whether you're doing it concurrently like with darolutamide or abiraterone or sequentially, like you saw today at Ian Davis's ENZAMET update with enzalutamide being used either concurrently or- as per the ARCHES study- sequentially. All of these are great options for this patient with high volume disease. One of the controversies for this patient would be whether he benefits from radiation to the primary. He had symptomatic disease, a big prostate, he's marginally high volume. The stampede data suggests that these patients may have an improved outcome by treating the primary. Certainly, that would be a source of resistance, where that could cause further dissemination and progression more rapidly. I would have that conversation with him. In the ARCHES trial, we showed that enzalutamide delays radiographic progression free survival that led to the FDA approval of that therapy. From the 5-year data that was presented at ASCO 2022, we see that many of these men are now being treated successfully for 5 plus years, still on drug and still going where medians haven’t even been reached. This is phenomenal for our patients. It emphasizes the need for survivorship. We haven’t necessarily worried as much about non-prostate cancer mortalities and the co-morbidity of these agents, but bone health and exercise, mental health, paying attention to cardiovascular risks, blood pressure monitoring. There's a lot of considerations now that neurologic oncologists, medical oncologists, community oncologists will need to pay attention to.

Evan Y. Yu, MD: I love the fact that you did a great summary there of all the systemic therapies and you brought in the idea of local radiation and the sub-group analysis from stampede and local therapy. How do you do this in your clinic? We all interact as medical oncologists, we're all medical oncologists here, but we have to interact and work closely with the surgeons, the urologists, and now radiation oncology, as there's increasing data there.

Transcript edited for clarity.

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