Bone Health Agents in Patients with Castrate-Resistant Prostate Cancer - Bertrand Tombal

January 16, 2020

Neal Shore and Bertrand Tombal discuss the importance of bone health agents, particularly in patients receiving castrate-resistant prostate cancer agents. Highlights of their conversation include the use of antiresorptive therapy to reduce the risk of skeletal-related events in men with bone mCRPC and decreased fracture rate by mandating bone-protecting agents in the EORTC 1333/PEACE III trial.


Bertrand Tombal, MD, PhD, Professor and Chairman, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Neal Shore, MD, Medical Director for the Carolina Urologic Research Center, Myrtle Beach, South Carolina, USA.

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Neal Shore: Hi, I'm Neal Shore. We're here in Basel, Switzerland for the third Advanced Prostate Cancer Consensus Conference. And what a great pleasure for me to be with my really dear friend and colleague, Bertrand Tombal. Bertrand and I, I think, we have been real champions for urologists to understand the importance of systemic therapy, and as well as doing great surgery. So thanks for being here.

Bertrand Tombal: My pleasure.

Neal Shore: Your presentation, which you gave a wonderful presentation on similar data at ASCO this year on the importance of bone health agents, particularly in patients receiving CRPC agents. So what are your thoughts?

Bertrand Tombal: Yeah. That's very interesting because you remember in 2004, 2005, we tested these drugs, zoledronic acid, denosumab, show patient would experience a lot of skeletal complications. But they were quite advanced patients and for an unknown reason, we never really use these drugs. Probably because they were not tested for overall survival. Then abi/enza came and now realized that we mostly abandoned these drugs. When you see that a trial like the, ERA 223 from Bayer, only 40% of the patient receives zoledronic acid or denosumab. Although they had extended bone metastasis. And actually we started realizing now that even, and even more in the era of abi/enza, Many of these patients have fractures and these fractures may actually increase mortality, and that we should start these drugs probably earlier to prevent fracture. Because they remain extremely effective. Knowing that the caveat is that we may treat too long.

And actually we realized that was drugs like abi/enza, that we've got a mixed of the traditional skeletal-related event, plus osteoporotic fractures. So maybe we shouldn't split these discussions between osteoporosis and skeletal-related events. But clearly we have now two trials, the ERA 223 trial and the [inaudible 00:02:12] trial with enzalutamide, that clearly showed that, even if you forget about radium, there's a very high risk of fracture that can be really well reduced by using denosumab or zoledronic acid. So I think that, for meeting like this, which is close to the community, these drugs may not be super fun, but they remain extremely important for the patient.

Neal Shore: So yeah. and maybe I'd like to hear you maybe kind of review some of the other top-line data that you did it at ASCO as well. But also, Bertrand, so then for our colleagues who are out there, if someone has bone metastatic CRPC, symptomatic or asymptomatic, and they're going to start on an androgen receptor blocker or a ligand inhibitor like abiraterone, what does the data tell us to do with a bone health agent?

Bertrand Tombal: I would say that, first, you should have been monitoring for osteoporosis while they were on ADT. So if you haven't done so, or if the colleague who referred the patient hasn't been doing so, start to do minimal like DEXA scan. That's the minimum. And then I usually look at how dominant the bone is. If the guy on top of that has elevated alkaline phosphatase, you've experienced a progression into few to multiple bone metastases. You should start the denosumab or zoledronic acid. And why not? This is something we don't have a lot of data.

If the patient responds very well, after a few months, maybe you can pose the drug. But I would say that the initiation of the treatment you should cover, because one of the observations we made is that these fractures, they happen within one year of treatment. So it's really, they should be covered at the initiation. And that would be my recommendation. Look at how dominant the bone is, if you have clear sign of progression in the bone, even more if alkaline phosphatase are elevated, start denosumab or zoledronic acid.

Neal Shore: So your comments about when we have patients on ADT for protracted time, and perhaps we haven't been giving them something like vitamin D calcium supplement, maybe we haven't talked to them about exercise systems exercise.

Bertrand Tombal: That's so important, yeah.

Neal Shore: And we still haven't even obtained a DEXA scan. The data in the SPARTAN, PROSPER and ARAMIS was rather remarkable at 10 to 3% in both arms. We're getting bone health agents.

Bertrand Tombal: Yeah, yeah. So that's really where we've missed. And that it's good that we had other sessions here, speaking about managing patient on ADT. And one of the number one consequences of how we treat the patient today, they live longer, but they don't live longer like this. They live longer with ADT. And ADT has become, really even more than before, the number one treatment. So following these patients closely, cardiovascular, like you spoke about, or bone, is extremely important.

Neal Shore: Fantastic. Thank you. Thank you very much.

Bertrand Tombal: Thank you.