Expanding Treatment Options for Metastatic CSPC

Transcript: Judd Moul, MD: I’d like to move on to the topic of metastatic castrate-sensitive prostate cancer [CSPC]. Because I’m the oldest member of the panel, I want to make a comment. I’ve been in the field long enough to remember the late ’80s and early ’90s, when flutamide was first FDA approved. Historically, that was for what, in those days, we called newly diagnosed D2 prostate cancer. That was before TNM [tumor, node, and metastasis] staging, so we now know it as newly diagnosed M1 [distant metastasis] or hormone-sensitive M1.

Back in the ’80s, Fernand Labrie, MD, PhD, from Canada was the first guy, to our knowledge, who talked about this concept of adrenal androgen suppression. He was touting flutamide, which is a not very potent oral antiandrogen. Ultimately, the National Cancer Institute [NCI] did the Crawford trial of leuprolide plus or minus flutamide versus placebo in newly diagnosed metastatic prostate cancer. The NCI did that trial to disprove Labrie because he was in Canada. He was an endocrinologist touting this concept, so the National Cancer Institute did that trial to prove him wrong. Lo and behold, they found that flutamide had a 7-month survival advantage, and that was the 1989 New England Journal of Medicine paper by E. David Crawford, MD. Flash forward 30 years, and finally, it looks like we’ve proven Labrie correct with these more potent agents.

Let’s get into metastatic castrate-sensitive prostate cancer. Alicia, first off, what is your current take on STAMPEDE and what the key teaching point of STAMPEDE is, related to a guy showing up in your clinic for the first time with newly diagnosed metastatic prostate cancer?

Alicia Morgans, MD, MPH: STAMPEDE, just to remind everybody, is an incredibly powerful multiarm trial in which everybody on the control arm gets best androgen suppression with an LHRH [luteinizing hormone-releasing hormone] agonist, antagonist, or orchiectomy. Then it has arm after arm that’s rolled out with different treatments for this metastatic hormone-sensitive population. One of the unique aspects of STAMPEDE is that it does have a small proportion of men who don’t truly have metastatic disease yet. They have nonmetastatic disease with a rising PSA [prostate-specific antigen], making them very high risk, and they have nodal involvement. It’s a bit of a heterogeneous population, but the majority of men in this are men who have metastatic hormone-sensitive disease.

The 2 arms that are of most value—actually 3, because there were 2 arms that had a docetaxel component—are the docetaxel, or docetaxel plus zoledronic acid arm, and the abiraterone arm, which both prolong survival in the metastatic hormone-sensitive setting compared with placebo. The docetaxel arms were published after the CHAARTED trial, which showed that chemo-hormonal therapy—6 cycles of docetaxel in addition to ADT [androgen deprivation therapy]—prolonged survival as compared with ADT alone. Then the abiraterone arm was concurrently published with the LATITUDE data that suggested a benefit in survival with abiraterone-ADT versus ADT alone.

Many questions have been raised around STAMPEDE. LATITUDE has this high-risk population, which is a little different from the high-volume population that was published in CHAARTED in the high-risk population. These are patients who had 3 bone metastases or more, a Gleason score that was higher than 8, and visceral involvement. They had to have 2 out of 3. There was clearly a benefit for abiraterone. In STAMPEDE, they looked and saw that this benefit appeared to hold for their entire population. It’s an important contribution that abiraterone, at least in the STAMPEDE trial, is helpful in terms of improving survival across all metastatic hormone-sensitive prostate cancer, not just in high-risk patients.

Then the CHAARTED study raises this question of high-volume disease versus low-volume disease with the benefit of chemotherapy—hormonal therapy being centered on high-volume disease in terms of prolonging survival, suggesting that it could be everyone. We expect that subgroup analysis to come out at ESMO [European Society for Medical Oncology Congress] 2019 looking at the STAMPEDE data by the CHAARTED subgroups to see if that benefit holds. What does STAMPEDE contribute to my decision making? It is immensely important as a uniting factor among all these different trials that are looking at different subgroups to understand the benefits of a multipronged, multimechanism approach to attacking metastatic hormone-sensitive disease.

I still think about high- and low-volume disease when I face a new patient with metastatic hormone-sensitive disease. I may be rethinking that when I see the STAMPEDE data in September of 2019, but I think that with high-volume patients with metastatic hormone-sensitive disease, if fit for chemotherapy, I have a conversation about chemotherapy—hormonal therapy and adding docetaxel. I also talk about abiraterone. For low-volume patients, I present only abiraterone-ADT. That’s a long answer, but it’s a very profound trial.

Judd Moul, MD: I want to get to the other panelists. The bottom line is, in your practice prior to ASCO [American Society of Clinical Oncology Annual Meeting] 2019, traditional ADT plus abiraterone was for low-volume disease. For high-volume disease, use traditional ADT and have the conversation to offer those patients 6 cycles of docetaxel.

Alicia Morgans, MD, MPH: Or abiraterone. Absolutely.

Judd Moul, MD: Or abiraterone. In high-volume disease, you want to have that conversation.

Alicia Morgans, MD, MPH: Absolutely.

Transcript Edited for Clarity