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Chemotherapy for BRCA-Mutated Prostate Cancer

Panelists: Joe OSullivan, MD, Queens University; Nicholas James, MBBS, PhD University of Birmingham; Noel Clarke, MBBS, Christie Hospital
Published: Thursday, Jan 03, 2019



Transcript:

Nicholas James, MD:
When we combined abiraterone [Zytiga] with radium, we had this unanticipated increase in bone toxicity. Additionally, we know that abiraterone has cardiac toxicity like PARP [poly (ADP ribose) polymerase] inhibitors. So I assume this is something that will be monitored very carefully.

Noel Clarke, MBBS, FRCS, ChM: Yes, and we know that abiraterone, for example, has an influence on DNA repair through the androgenic axis. This may be influential; we just don’t know. We’re in the realm of speculation and need to gather more data.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: This has been an extremely informative discussion. Before we end our discussion, I’d like to get closing thoughts from each of you. Professor Clarke, would you provide a closing state of the future of prostate cancer treatment?

Noel Clarke, MBBS, FRCS, ChM: Well, it’s a continually moving field, and this is great. So obviously, we’re particularly excited by the data we were able to present at the European Society of Medical Oncology [ESMO] 2018 Annual Meeting, which has helped us to begin understanding what we mean by oligometastatic disease. We have a lot of work to do on tumor loads, and I think my take-home comment from the ESMO meeting has been that we now have a better [understanding] of high and low disease burden and what the threshold is for local treatment.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Nick?

Nicholas James, MD: I think that the M1RT [multidimensional item repo component] data from STAMPEDE should change practice for oligometastatic patients. I think the take-home message for me from the ERA 223 trial is that it really underscores the fact that with longer survival with bone-damaging agents, you have to be aware of what you’re doing to the normal skeleton, let alone what you’re doing to the disease. Obviously, it also shows you shouldn’t coadminister abiraterone and radium starting at the same time—whether it does much else to the radium is debatable. The other thing from the BRCA discussion we’ve been having is that new targets are emerging as well, which are potentially very interesting.
Although they weren’t presented at ESMO, there are very clear data emerging now that stereotactic body radiotherapy for oligometastatic disease—we defined an oligometastatic group in STAMPEDE—will prolong survival. We’re going to put those 2 things together and look at stereotactic body radiotherapy and treat the primary group as the next step in STAMPEDE trial.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Exciting times for radiation oncology.

Nicholas James, MD: Absolutely.

Noel Clarke, MBBS, FRCS, ChM: I might just add one final thought. Don’t forget the [immunologic]-immunotherapy axis, because I don’t think that story is over.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Well, thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us and hope you found this OncLive® Peer Exchange® to be useful and informative.

Transcript Edited for Clarity.

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Transcript:

Nicholas James, MD:
When we combined abiraterone [Zytiga] with radium, we had this unanticipated increase in bone toxicity. Additionally, we know that abiraterone has cardiac toxicity like PARP [poly (ADP ribose) polymerase] inhibitors. So I assume this is something that will be monitored very carefully.

Noel Clarke, MBBS, FRCS, ChM: Yes, and we know that abiraterone, for example, has an influence on DNA repair through the androgenic axis. This may be influential; we just don’t know. We’re in the realm of speculation and need to gather more data.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: This has been an extremely informative discussion. Before we end our discussion, I’d like to get closing thoughts from each of you. Professor Clarke, would you provide a closing state of the future of prostate cancer treatment?

Noel Clarke, MBBS, FRCS, ChM: Well, it’s a continually moving field, and this is great. So obviously, we’re particularly excited by the data we were able to present at the European Society of Medical Oncology [ESMO] 2018 Annual Meeting, which has helped us to begin understanding what we mean by oligometastatic disease. We have a lot of work to do on tumor loads, and I think my take-home comment from the ESMO meeting has been that we now have a better [understanding] of high and low disease burden and what the threshold is for local treatment.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Nick?

Nicholas James, MD: I think that the M1RT [multidimensional item repo component] data from STAMPEDE should change practice for oligometastatic patients. I think the take-home message for me from the ERA 223 trial is that it really underscores the fact that with longer survival with bone-damaging agents, you have to be aware of what you’re doing to the normal skeleton, let alone what you’re doing to the disease. Obviously, it also shows you shouldn’t coadminister abiraterone and radium starting at the same time—whether it does much else to the radium is debatable. The other thing from the BRCA discussion we’ve been having is that new targets are emerging as well, which are potentially very interesting.
Although they weren’t presented at ESMO, there are very clear data emerging now that stereotactic body radiotherapy for oligometastatic disease—we defined an oligometastatic group in STAMPEDE—will prolong survival. We’re going to put those 2 things together and look at stereotactic body radiotherapy and treat the primary group as the next step in STAMPEDE trial.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Exciting times for radiation oncology.

Nicholas James, MD: Absolutely.

Noel Clarke, MBBS, FRCS, ChM: I might just add one final thought. Don’t forget the [immunologic]-immunotherapy axis, because I don’t think that story is over.

Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Well, thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us and hope you found this OncLive® Peer Exchange® to be useful and informative.

Transcript Edited for Clarity.
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