Read the Full Video Transcript

Leslie Ballas: Hi. Welcome to ASCO GU. I'm Leslie Ballas. I'm a radiation oncologist at Cedars-Sinai. And I am lucky to be joined this morning by Dr. Neil Desai who is a radiation oncologist at UT Southwestern and who is going to talk to us today about his abstract-- evaluating the combination of radiotherapy with antibody drug conjugates in advanced urothelial carcinoma, as well as other diseases. Thank you for joining us today, Neil.

Neil Desai: Thank you.

Leslie Ballas: I just wanted to first have you tell us a little bit about this abstract and why you engaged in this work.

Neil Desai: Certainly. So as we all know, the antibody drug conjugates are changing the landscape of advanced urothelial carcinoma. The various agents are being used. We don't know how they interact with radiotherapy, which is still an important part of our compendium of palliative treatments as well as increasingly used for durable disease control. And so the question is, do these toxins or antibody drug conjugates with these payloads of anti-cancer drugs, are they going to interact in an adverse way with radiotherapy?

And this has driven understandable fear on behalf of patients to want to be safe. And do we use radiation? Do we stop systemic therapy to use radiation and risk systemic progression? We want to answer that question in a practical, real-world scenario. So that was a reason for the study.

Leslie Ballas: Now in the study, you talk about palliative radiotherapy in combination with these ADCs. In radiotherapy, when we palliate patients, we sometimes use standard dosing and sometimes we use a stereotactic approach. A lot of times, we're seeing patients who've responded really well to ADCs but who have one site of oligoprogression. Did you happen to look at the difference between a standard palliative approach and a stereotactic approach?

Neil Desai: Yeah, a great question, not all radiotherapy is the same. And so we looked at not just a sequence of radiation, whether it was before or during or after the infusions of antibody drug conjugates, which had no interaction with side effects or risk of them. We also looked at, you said, different dosing levels or intensities of radiotherapy.

Broadly, many folks will divide this into whether you're doing palliative, hypofractionated radiotherapy over 10 days, for instance, which might be lower dose, and to just control pain compared to higher dose per day radiation over one to five treatments, which have been codified as something called stereotactic body radiotherapy. And that might have higher side effects despite the increasing precision in therapy.

And so we looked at those. And about a third of patients did indeed have a higher dose per day radiation, what we call higher intensity radiation. And this did not seem to have any interaction with side effect profile. When we looked at specifically those patients who stopped ADCs due to dose-limiting toxicities, which you commonly see with these agents, none of them really seem to be increased or in the field of where radiation was given, whether or not you're at higher dose.

Leslie Ballas: And I realized, as a radiation oncologist, I jumped right into a radiation question. And I didn't give you the opportunity to tell us what was your general conclusion in this study? And are ADCs safe to give concurrently or in the peri-radiation period?

Neil Desai: Yes, with all the caveats as you know very well with our real-world retrospective data, which spanned everything from pre to post to concurrent dosing array of therapy in these agents, there didn't seem to be any increased signal for adverse events related to toxicities known for these agents or unknown to these agents in field or out of field. Of the 10 patients who had dose limiting toxicities requiring suspension of those infusions of ADCs, only one had potential contribution of radiation. And that was a very special scenario, a very broad field craniospinal radiation, which maybe contributed to marrow suppression. But this would be expected in itself from concurrent spinal radiation. Otherwise, we found no reason to believe that these agents shouldn't be combined.

Now, where does this lead us? We want to be aware of, not only use of radiation for palliative purposes, for disease control, what about curative intent therapies? There were about 10% of patients who had bladder intact being irradiated in the study with concurrent ADCs. Again, we didn't see any signal for adverse events being increased by the conjunction of ADCs radiation even when given to the bladder itself.

Leslie Ballas: So how do we apply this data today? Can this affect patients? For providers who are watching us have this conversation, do you feel that we're ready to be overlapping radiation with ADCs?

Neil Desai: Certainly, I think we want to be judicious and careful like any systemic therapy combinations of radiation. But with the dosing regimens of radiation we use concurrently with EV and SG on this study, there doesn't seem to be any reason to hold back on palliative radiation. So that's number one takeaway is palliate your patients. Treat them for what they need to be having done with those same radiation approaches you would use otherwise without concern for stopping systemic therapy. That would be perhaps an unnecessary risk to take in forgoing systemic control. That's number one takeaway.

Number two, probably as important takeaway is informing studies of combination of these agents for curative intent therapies, which are ongoing now. And at least one study, at least at our institution, has been informed by this data. So this is very practical takeaway. We need this data to show safety in the first place.

Leslie Ballas: Well, congratulations on a wonderful abstract and for helping move the field forward. I really appreciate you taking the time.

Neil Desai: Thank you. Thank you for collaborating on this study of course.